# U.S. Route 21

U.S. Route 21 or U.S. Highway 21 (US 21) is a north–south United States Numbered Highway, spanning 393 miles (632 km) from Hunting Island State Park, South Carolina, to Wytheville, Virginia. The route traverses three states, South Carolina, North Carolina, and Virginia. It connects southeastern cities, including Columbia, South Carolina, and Charlotte, North Carolina.
US 21 starts at Hunting Island State Park, bypasses Beaufort, South Carolina, and then heads north across the low country, paralleling Interstate 77 (I-77) through urban and rural areas before entering North Carolina. In North Carolina, US 21 frequently merges with and splits from I-77. The route enters Virginia, passing through hilly terrain before ending at the intersection of Interstate 81 (I-81) / U.S. Route 52 (US 52) in Wytheville.
Despite the "1" indicating that it is a major north–south highway, US 21 only travels through three states and is no longer a cross-country route, as many sections have been replaced by I-77 in Ohio and West Virginia. Historically, US 21 was longer before the Interstate Highway System was established. US 21 originally ran from Cleveland, Ohio, to Yemassee, South Carolina, it was later extended to Beaufort and Hunting Island State Park. Over time, its length was reduced, making it the second-shortest major north–south route after U.S. Route 91 (US 91).
US 21 serves as an alternative to the more heavily trafficked interstates in the area, particularly I-77, I-26, and Interstate 95 (I-95).

## Route description

Lengths :
| | mi | km |
| SC | 233 | 375 |
| NC | 125 | 201 |
| VA | 35 | 56 |
| Total | 393 | 632 |

### South Carolina

US 21 travels 233.2 miles (375.3 km) through the state. Beginning at Hunting Island State Park, US 21 travels west toward Beaufort, where it widens to four lanes. The route bypasses Beaufort to the south, going through Port Royal, Shell Point, and Burton. In the Beaufort area, US 21 passes by the entrances to Parris Island and Marine Corps Air Station Beaufort, the major Marine Corps installations in the area. North of Beaufort, US 21 continues as a four-lane divided highway and intersects with US 17. The route travels in a wrong-way concurrency with US 17 south for seven miles (11 km) before turning north toward Yemassee, where it becomes a rural two-lane road and intersects with US 17 Alternate. North of Yemassee, US 21 splits off and crosses I-95 at exit 42.
The two-lane route continues through rural portions of the state. US 21 goes through Smoaks and Branchville and bypasses Orangeburg. North of Orangeburg, US 21 runs roughly parallel to I-26 until Gaston where it conjoins US 321 and becomes an urban highway. US 21 passes through Cayce, West Columbia, and Columbia.
North of Columbia, US 21 splits from US 321, reverting to a rural two-lane road parallel to I-77. In York County, US 21 enters urban areas again, connecting Rock Hill and Fort Mill. Near the North Carolina state line, US 21 merges with I-77 near Carowinds, then enters North Carolina.

### North Carolina

US 21 begins as a concurrency with I-77 in Charlotte, which it repeats three times within the state. Its first break with I-77 is along Statesville Avenue, then proceeding through Huntersville and Cornelius, however, because of its close proximity to I-77 and North Carolina Highway 115 (NC 115), it has no interchange with I-485 by itself. The second break with I-77 occurs at Mooresville, where US 21 travels through the city and then northwest into Statesville. After Statesville, US 21 travels northeast to Harmony and Brooks Crossroads, before merging back with I-77 near Jonesville. However, Jonesville and Elkin connect with US 21 Bus. through centers of both towns, as an alternate route paralleling I-77. North of Elkin, US 21 splits with I-77 for the last time and goes north to Sparta, passing the Blue Ridge Parkway after a major, curvy section. North of Sparta, at Twin Oaks, US 221 overlaps with US 21 before entering Virginia. US 21 travels 124.5 miles (200.4 km) through the western Piedmont of North Carolina, either combined with I-77 or as a two-lane rural road; from the South Carolina state line to Elkin, travelers can easily skip a majority of US 21 via I-77.

### Virginia

After a few miles crossing the state line, US 21 reaches the town of Independence, where it splits with US 221 and continues north. The route goes through the Mount Rogers National Recreation Area before entering the city of Wytheville. After a short concurrency with US 11 in downtown Wytheville, it goes north and ends at the intersection of I-81/US 52. US 21 travels 35 miles (56 km) through western Virginia, mostly as a two-lane rural mountain road.

## History

US 21 in the pre-Interstate era was a north–south highway connecting the area around Lake Erie and the coastal South. One of the few true north–south routes to cross the middle Appalachian Mountains, it became an important corridor for motor traffic between northeastern Ohio, western Pennsylvania, (with US 19) and western New York with central North Carolina, central and southeastern South Carolina, and (by connecting with other highways) coastal Georgia and most of Florida. Many referred to the stretch of US 21 from the Great Lakes Region to Florida as "The Lakes-to-Florida Highway".
US 21 originally (in 1926) connected Cleveland, Ohio, and Yemassee, South Carolina. In 1935 it was extended to Beaufort, South Carolina, and again in 1953 to its current southern terminus at the Atlantic Coast at Hunting Island State Park, between the city of Beaufort and Fripp Island.
In the Interstate Highway era, much of US 21 became an obvious corridor for a long-distance expressway. The West Virginia Turnpike between Charleston, West Virginia, and Princeton, West Virginia, was the first segment of a planned series of toll highways along or near US 21 from Cleveland to Charlotte, North Carolina. All the other toll highways were shelved in favor of freeways built with Interstate funding; these freeways and the West Virginia Turnpike became I-77, which completely supplanted old US 21 as a long-distance through route. I-77 was later extended to Columbia, South Carolina, also within a few miles of US 21.
Between Cleveland and Charleston, all but a relatively short segment of US 21 was completely deleted in favor of I-77, the relics being as follows:
* State Route 21 (SR 21) between Cuyahoga Heights and Strasburg;
* SR 821 between I-77 near Byesville and SR 60 near Marietta, Ohio;
* County Road 35 (CR 35, Oakwood Road, Byesville Road, Old Twenty-One Road) between Byesville and the Guernsey–Tuscarawas county line;
* CR 3 (Salt Fork Road) between the Guernsey–Tuscarawas county line to SR 258
* CR 21 between Newcomerstown and New Philadelphia
* County Route 21 (CR 21) between Mineral Wells and Charleston.
Between Charleston and its current northern terminus at Wytheville, Virginia, almost all of US 21 ran concurrently with either US 60, US 19, or US 52, which remained as US 21 was deleted. The short segment of US 21 in southern West Virginia not coinciding with another U.S. Highway became an extension of West Virginia Route 16.
In North Carolina, US 21 originally entered the state along today's NC 51 into Pineville, then followed Old Pineville Road into Charlotte. In the mid-1930s, US 21 moved over to South Boulevard from Old Pineville Road. In 1969, US 21 was rerouted following today's I-77 alignment, the old route was replaced by an extension of US 521. From 1975–1987, US 21 moved north in segments onto I-77 to its current alignment ending at exit 16A (Sunset Road). Further north, US 21 originally followed Old Statesville Road, replaced in 1956 by NC 115. In 1966, US 21 was bypassed around Jonesville and Elkin, replaced with US 21 Bus.
US 21 in Beaufort, South Carolina, was rerouted around the city over former SC 280 as well as a portion of SC 802. The new routing went into effect on February 26, 2012.
Browse numbered routes :
| ← US 20A | OH | → SR 21 |

## Major intersections

| State | County | Location | mi | km | Exit | Destinations | Notes |
| South Carolina | Beaufort | Hunting Island State Park | 0.00 | 0.00 | | Sea Island Parkway / Campground Road | Southern terminus; road continues as Sea Island Parkway |
| South Carolina | Beaufort | Lady's Island | 14.50 | 23.34 | | US 21 Bus. north (Sea Island Parkway west) / SC 802 east (Sams Point Road) | Southern terminus of US 21 Bus.; western terminus of SC 802 |
| South Carolina | Beaufort | Port Royal | 17.35 | 27.92 | | SC 281 north (Ribaut Road north) | Southern terminus of SC 281 |
| South Carolina | Beaufort | Port Royal | 19.87 | 31.98 | | Parris Island M.C.R.D. | Interchange |
| South Carolina | Beaufort | Port Royal | 21.10 | 33.96 | | SC 128 west (Savannah Highway) – Bluffton, Hardeeville, Hilton Head Island | Eastern terminus of SC 128 |
| South Carolina | Beaufort | Beaufort | 24.24 | 39.01 | | SC 170 (Robert Smalls Parkway) – Beaufort | |
| South Carolina | Beaufort | Burton | 25.44 | 40.94 | | US 21 Bus. south – Beaufort | Northern terminus of US 21 Bus. |
| South Carolina | Beaufort | Burton | 26.86 | 43.23 | | SC 116 west – Laurel Bay | Eastern terminus of SC 116 |
| South Carolina | Beaufort | Gardens Corner | 37.40 | 60.19 | | US 17 north – Charleston | Interchange; eastern end of US 17 concurrency |
| South Carolina | Beaufort | Pocotaligo | 44.00 | 70.81 | | US 17 Alt. begins / US 17 south to I-95 – Ridgeland, Savannah | Western end of US 17 concurrency; southern end of US 17 Alt. concurrency; southern terminus of US 17 Alt. |
| South Carolina | Hampton | Yemassee | 47.77 | 76.88 | | SC 68 west (Connely Street) / Flowers Street south (US 17 Conn. south) to I-95 – Hampton, Allendale | Eastern terminus of SC 68; northern terminus of US 17 Conn. |
| South Carolina | Colleton | ​ | 49.39 | 79.49 | | US 17 Alt. north (Hendersonville Highway) – Walterboro | Northern end of US 17 Alt. concurrency |
| South Carolina | Colleton | ​ | 52.04 | 83.75 | | I-95 – Florence, Savannah | I-95 exit 42 |
| South Carolina | Colleton | ​ | 62.00 | 99.78 | | SC 63 (Sniders Highway) – Varnville, Walterboro | |
| South Carolina | Colleton | Bells Crossroads | 68.41 | 110.10 | | SC 64 (Bells Highway) – Ehrhardt, Walterboro | |
| South Carolina | Colleton | Smoaks | 77.10 | 124.08 | | SC 217 (Lodge Highway) – Lodge | |
| South Carolina | Bamberg | Whetstone Crossroads | 83.20 | 133.90 | | SC 61 (Edisto River Road) – Bamberg | |
| South Carolina | Orangeburg | Branchville | 88.65 | 142.67 | | US 78 west (Edward Street) – Bamberg | Southern end of US 78 concurrency |
| South Carolina | Orangeburg | Branchville | 88.85 | 142.99 | | US 78 east (Dorange Road) – Charleston | Northern end of US 78 concurrency |
| South Carolina | Orangeburg | Branchville | 89.26 | 143.65 | | SC 210 north – Bowman | Southern terminus of SC 210 |
| South Carolina | Orangeburg | Orangeburg | 104.16 | 167.63 | | US 21 Bus. north (Rowesville Road) / Stonewall Jackson Boulevard (US 601 Truck north / SC 4 west) | Southern end of US 601 Truck concurrency; southern terminus of US 21 Bus.; eastern terminus of SC 4 |
| South Carolina | Orangeburg | Orangeburg | 104.23 | 167.74 | | US 178 east (Charleston Highway east) / US 178 Bus. west (Charleston Highway west) – Charleston | Southern end of US 178 concurrency; eastern terminus of US 178 Bus. |
| South Carolina | Orangeburg | Orangeburg | 105.55 | 169.87 | | US 301 (Five Chop Road) – Santee, Bamberg | |
| South Carolina | Orangeburg | Orangeburg | 105.65 | 170.03 | | SC 33 (Russel Street) – Cameron | |
| South Carolina | Orangeburg | Orangeburg | 107.50 | 173.00 | | US 601 (Magnolia Street) / US 601 Truck ends – St. Matthews, Bamberg | Northern end of US 601 Truck concurrency; northern terminus of US 601 Truck |
| South Carolina | Orangeburg | Orangeburg | 108.59 | 174.76 | | US 178 west (Chestnut Street) / Columbia Road south (US 21 Conn. south) – North | Northern end of US 178 concurrency; northern terminus of US 21 Conn.; US 21 turns right off of Chestnut Street and onto Columbia Road. |
| South Carolina | Calhoun | ​ | 120.48 | 193.89 | | SC 172 – North | |
| South Carolina | Calhoun | ​ | 120.58 | 194.05 | | SC 6 east to I-26 | Southern end of SC 6 concurrency |
| South Carolina | Calhoun | ​ | 122.15 | 196.58 | | SC 6 north (Center Hill Road) – Swansea | Northern end of SC 6 concurrency |
| South Carolina | Lexington | ​ | 127.48 | 205.16 | | I-26 – Columbia, Charleston | I-26 exit 129 |
| South Carolina | Calhoun | Sandy Run | 130.23 | 209.58 | | US 176 east (Old State Road) – St. Matthews | Southern end of US 176 concurrency |
| South Carolina | Lexington | ​ | 137.13 | 220.69 | | I-26 – Columbia, Charleston | I-26 exit 119 |
| South Carolina | Lexington | ​ | 138.98 | 223.67 | | US 321 south – Gaston, Swansea | Southern end of US 321 concurrency |
| South Carolina | Lexington | Cayce | 141.48 | 227.69 | | I-77 north – Charlotte | I-77 exit 1 |
| South Carolina | Lexington | Cayce | 141.87 | 228.32 | | I-26 – Charleston, Spartanburg | I-26 exit 115 |
| South Carolina | Lexington | Cayce | 142.97 | 230.09 | | SC 2 north (Frink Road) | Southern terminus of SC 2 |
| South Carolina | Lexington | West Columbia | 144.45 | 232.47 | | SC 302 south (Airport Boulevard) – Aiken, Columbia Airport | Northern terminus of SC 302 |
| South Carolina | Lexington | Cayce | 146.23 | 235.33 | | SC 2 (State Street) | |
| South Carolina | Richland | Columbia | 147.22 | 236.93 | | SC 48 Truck east (Blossom Street / US 21 Conn. east / US 76 Conn. east) to US 76 east / US 378 east | Western terminus of US 21 Conn., US 76 Conn., and SC 48 Truck; US 21, US 176, and US 321 turn left off of Blossom Street and onto Huger Street. |
| South Carolina | Richland | Columbia | 147.86 | 237.96 | | US 1 / US 378 (Gervais Street) – South Carolina State Museum, Confederate Relic Room, EdVenture, Columbia SC Visitors Center, Convention Center, Colonial Life Arena | |
| South Carolina | Richland | Columbia | 148.16 | 238.44 | | SC 12 east (Hampton Street) – Fort Jackson | One-way couplet |
| South Carolina | Richland | Columbia | 148.26 | 238.60 | | SC 12 west (Taylor Street) – Lexington | One-way couplet |
| South Carolina | Richland | Columbia | 148.76 | 239.41 | | I-126 west / US 76 west to I-20 – Greenville, Spartanburg | Southern end of I-126/US 76 concurrency; Rep. T. Moffatt Burriss Sr. Interchange |
| South Carolina | Richland | Columbia | 149.08 | 239.92 | | I-126 ends | Northern end of I-126 concurrency |
| South Carolina | Richland | Columbia | 149.38 | 240.40 | | SC 48 east (Assembly Street) – Columbia Museum of Art | Western terminus of SC 48 |
| South Carolina | Richland | Columbia | 149.46 | 240.53 | | US 76 east (Elmwood Avenue) | Northern end of US 76 concurrency |
| South Carolina | Richland | Columbia | 149.97 | 241.35 | | US 176 west (River Drive) | Northern end of US 176 concurrency |
| South Carolina | Richland | Columbia | 150.66 | 242.46 | | SC 16 (Sunset Drive) | |
| South Carolina | Richland | Columbia | 151.23 | 243.38 | | SC 215 north (Monticello Road) | Southern terminus of SC 215 |
| South Carolina | Richland | Columbia | 152.22 | 244.97 | | US 321 north (Fairfield Street) – Winnsboro | Northern end of US 321 concurrency |
| South Carolina | Richland | Columbia | 154.76 | 249.06 | | I-20 – Florence, Augusta | I-20 exit 71 |
| South Carolina | Richland | Blythewood | 162.17 | 260.99 | | I-77 – Columbia, Charlotte | I-77 exit 24 |
| South Carolina | Richland | Blythewood | 163.46 | 263.06 | | SC 555 (Farrow Road) – Columbia | |
| South Carolina | Fairfield | ​ | 171.40 | 275.84 | | Coleman Highway west (US 21 Conn. north) – Winnsboro | Southern terminus of US 21 Conn.; eastern terminus of Coleman Highway |
| South Carolina | Fairfield | Ridgeway | 172.09 | 276.95 | | SC 34 east (Palmer Street) – Lugoff, Camden | Southern end of SC 34 concurrency |
| South Carolina | Fairfield | Ridgeway | 172.31 | 277.31 | | SC 34 west (Church Street) – Winnsboro Mills | Northern end of SC 34 concurrency |
| South Carolina | Fairfield | ​ | 189.11 | 304.34 | | SC 200 – Winnsboro | Southern end of SC 200 concurrency |
| South Carolina | Chester | Great Falls | 192.07 | 309.11 | | SC 99 north (Chester Avenue) – Richburg | Southern terminus of SC 99 |
| South Carolina | Chester | Great Falls | 193.29 | 311.07 | | SC 97 north – Chester | Southern end of SC 97 concurrency |
| South Carolina | Chester | Great Falls | 193.43 | 311.30 | | SC 97 south / SC 200 north – Lancaster | Northern end of SC 97 and SC 200 concurrencies |
| South Carolina | Chester | Fort Lawn | 200.93 | 323.37 | | SC 9 (Chester Avenue) – Richburg, Lancaster | |
| South Carolina | Chester | ​ | 206.23 | 331.90 | | SC 223 (Wylies Mill Road) – Richburg | |
| South Carolina | York | ​ | 213.55 | 343.68 | | SC 5 south – Lancaster | Interchange; southern end of SC 5 concurrency; to Andrew Jackson State Park |
| South Carolina | York | Lesslie | 215.67 | 347.09 | | Lesslie | Interchange via connector road |
| South Carolina | York | Rock Hill | 217.26 | 349.65 | | Lesslie, Red River | Interchange |
| South Carolina | York | Rock Hill | 218.02 | 350.87 | | I-77 – Columbia, Charlotte | I-77 exit 77 |
| South Carolina | York | Rock Hill | 218.72 | 352.00 | | SC 5 / SC 121 (Main Street) | Access to Piedmont Medical Center; northern end of SC 5 concurrency; southern end of SC 121 concurrency |
| South Carolina | York | Rock Hill | 220.20 | 354.38 | | SC 122 (Dave Lyle Boulevard) to I-77 | Interchange |
| South Carolina | York | Rock Hill | 222.36 | 357.85 | | SC 322 west (Cherry Road west) / SC 121 ends | Northern end of SC 121 concurrency; northern terminus of SC 121; eastern terminus of SC 322 |
| South Carolina | York | Rock Hill | 222.80 | 358.56 | | I-77 – Columbia, Charlotte | I-77 exit 82 |
| South Carolina | York | Rock Hill | 223.00 | 358.88 | | SC 161 north (Celanese Road) to I-77 north – Charlotte, York | Southern terminus of SC 161 |
| South Carolina | York | Fort Mill | 224.37 | 361.09 | | US 21 Bus. north (Spratt Street) – Fort Mill | Southern terminus of US 21 Bus. |
| South Carolina | York | Fort Mill | 226.42 | 364.39 | | SC 160 – Tega Cay | |
| South Carolina | York | Fort Mill | 229.20 | 368.86 | | SC 460 (Springfield Parkway) – Tega Cay, Fort Mill | |
| South Carolina | York | Fort Mill | 230.35 | 370.71 | | US 21 Bus. south (Old Nation Road) | Northern terminus of US 21 Bus. |
| South Carolina | York | Fort Mill | 231.14 | 371.98 | | SC 51 north (Pineville–Rock Hill Road) – Pineville | Southern terminus of SC 51 (northern segment) |
| South Carolina | York | Fort Mill | 231.89 | 373.19 | | I-77 south – Columbia | Southern end of I-77 concurrency; I-77 exit 90 |
| | | | 232.520.00 | 374.200.00 | | South Carolina–North Carolina line | South Carolina–North Carolina line |
| North Carolina | Mecklenburg | Charlotte | 0.9 | 1.4 | 1A | Westinghouse Boulevard | Exit numbers follow I-77 |
| North Carolina | Mecklenburg | Charlotte | 1.8 | 2.9 | 1B | I-485 – Huntersville, Pineville | Formerly exit 2 (southbound) before August 2010; I-485 exit 67 |
| North Carolina | Mecklenburg | Charlotte | 2.8 | 4.5 | 3 | Arrowood Road | Formerly exit 2 (northbound) before August 2010 |
| North Carolina | Mecklenburg | Charlotte | 3.7 | 6.0 | 4 | Nations Ford Road | |
| North Carolina | Mecklenburg | Charlotte | 4.8 | 7.7 | 5 | Tyvola Road | Single-point urban interchange |
| North Carolina | Mecklenburg | Charlotte | 6.0 | 9.7 | 6A | Woodlawn Road south (Charlotte Route 4 east) – Queens University | To Pfeiffer University |
| North Carolina | Mecklenburg | Charlotte | 6.2 | 10.0 | 6B | To NC 49 (S. Tryon Street) / Billy Graham Parkway (Charlotte Route 4 west) | To Billy Graham Library and Charlotte Douglas International Airport; southbound signed as NC 49 south (S. Tryon St. south) only |
| North Carolina | Mecklenburg | Charlotte | 7.3 | 11.7 | 7 | To NC 49 / Clanton Road | |
| North Carolina | Mecklenburg | Charlotte | 8.3 | 13.4 | 8 | To NC 160 / Remount Road | Northbound exit and southbound entrance |
| North Carolina | Mecklenburg | Charlotte | 9.0 | 14.5 | 9A | NC 160 (West Boulevard) | Southbound exit and northbound entrance; access from collector-distributor lanes |
| North Carolina | Mecklenburg | Charlotte | 9.4 | 15.1 | 9B | I-277 north / US 74 east (John Belk Freeway) | Access from collector-distributor lanes; I-277 exits 1B-C |
| North Carolina | Mecklenburg | Charlotte | 9.5 | 15.3 | 9C | US 74 west (Wilkinson Boulevard) to US 29 / NC 27 | US 29 and NC 27 signed northbound only; access from collector-distributor lanes; US 74 exits 1B-C |
| North Carolina | Mecklenburg | Charlotte | 9.9 | 15.9 | 10A | US 29 / NC 27 (Morehead Street) | Southbound exit and northbound entrance |
| North Carolina | Mecklenburg | Charlotte | 10.4 | 16.7 | 10 | Trade Street / Fifth Street | Signed southbound as exits 10B (Trade Street east) and 10C (Fifth Street/Trade Street west) |
| North Carolina | Mecklenburg | Charlotte | 11.0 | 17.7 | 11A | I-277 south / NC 16 south (Brookshire Freeway east) – Downtown Charlotte | I-277 exits 5A-B |
| North Carolina | Mecklenburg | Charlotte | 11.2 | 18.0 | 11B | NC 16 north (Brookshire Freeway west) | Left exit northbound; NC 16 exits 5A-B |
| North Carolina | Mecklenburg | Charlotte | | | — | I-77 north (Express lanes) | Southern terminus of HOV3+/toll lanes |
| North Carolina | Mecklenburg | Charlotte | | | — | I-277 south | Express lanes only, southbound exit and northbound entrance |
| North Carolina | Mecklenburg | Charlotte | 12.4 | 20.0 | 12 | Lasalle Street / Atando Avenue | |
| North Carolina | Mecklenburg | Charlotte | 13.3 | 21.4 | 13 | I-85 – Greensboro, Spartanburg | Signed as exits 13A (north) and 13B (south); hybrid interchange; I-85 exit 38 |
| North Carolina | Mecklenburg | Charlotte | | | — | I-85 north | Express lanes only; northbound exit and southbound entrance |
| North Carolina | Mecklenburg | Charlotte | 15.8 | 25.4 | | I-77 north – Statesville | Northern end of I-77 concurrency; I-77 exit 16 |
| North Carolina | Mecklenburg | Charlotte | 16.3 | 26.2 | | NC 115 north (Old Statesville Road) | Southern terminus of NC 115 |
| North Carolina | Mecklenburg | Charlotte | 18.9 | 30.4 | | NC 24 (W.T. Harris Boulevard) | To Northlake Mall |
| North Carolina | Mecklenburg | Huntersville | | | | Alexandriana Road to I-485 | |
| North Carolina | Mecklenburg | Huntersville | 25.7 | 41.4 | | NC 73 (Sam Furr Road) – Concord | |
| North Carolina | Mecklenburg | Cornelius | 28.8 | 46.3 | | I-77 south – Charlotte | Southern end of I-77 concurrency; I-77 exit 28 |
| North Carolina | Mecklenburg | Davidson | 30.2 | 48.6 | 30 | Griffith Street – Davidson | Exit numbers follow I-77 |
| North Carolina | Lake Norman | Lake Norman | | | Lake Norman Causeway | Lake Norman Causeway | Lake Norman Causeway |
| North Carolina | Iredell | Mooresville | 32.1 | 51.7 | 31 | Langtree Road | |
| North Carolina | Iredell | Mooresville | 33.7 | 54.2 | | I-77 north – Statesville | Northern end of I-77 concurrency; I-77 exit 33 |
| North Carolina | Iredell | Mooresville | 36.4 | 58.6 | | NC 150 (Plaza Drive) | Interchange |
| North Carolina | Iredell | Mooresville | 39.1 | 62.9 | | NC 115 south (Statesville Highway) | Southern end of NC 115 concurrency |
| North Carolina | Iredell | ​ | 43.3 | 69.7 | | I-77 – Charlotte, Statesville | I-77 exit 42 |
| North Carolina | Iredell | Statesville | 51.2 | 82.4 | | US 70 (Garner Bagnal Boulevard) – Conover, Salisbury | |
| North Carolina | Iredell | Statesville | 51.9 | 83.5 | | US 64 west (Front Street) / NC 115 north (Center Street) | Northern end of NC 115 concurrency; southern end of US 64 concurrency |
| North Carolina | Iredell | Statesville | 52.3 | 84.2 | | NC 90 west (Water Street) | Eastern terminus of NC 90 |
| North Carolina | Iredell | Statesville | 53.2 | 85.6 | | US 64 east (Davie Avenue) – Mocksville | Northern end of US 64 concurrency |
| North Carolina | Iredell | Statesville | 54.1 | 87.1 | | I-40 – Hickory, Winston-Salem | I-40 exit 151 |
| North Carolina | Iredell | ​ | 57.2 | 92.1 | | I-77 – Statesville, Elkin | I-77 exit 54 |
| North Carolina | Iredell | Harmony | 66.9 | 107.7 | | NC 901 (Memorial Highway) – Union Grove | |
| North Carolina | Yadkin | Brooks Crossroads | 79.2 | 127.5 | | US 421 – Wilkesboro, Yadkinville, Winston-Salem | |
| North Carolina | Yadkin | ​ | 85.4 | 137.4 | | I-77 south / US 21 Bus. north – Statesville, Jonesville | Southern end of I-77 concurrency; I-77 exit 79; southern terminus of US 21 Bus. |
| North Carolina | Yadkin | Jonesville | 88.5 | 142.4 | 82 | NC 67 – Jonesville, Boonville, Elkin | Exit number follows I-77 |
| North Carolina | Yadkin River | Yadkin River | | | Sgt. Gregory Keith Martin Memorial Bridges | Sgt. Gregory Keith Martin Memorial Bridges | Sgt. Gregory Keith Martin Memorial Bridges |
| North Carolina | Surry | Elkin | 90.3 | 145.3 | | I-77 north – Wytheville | Northern end of I-77 concurrency; southbound exit and northbound entrance; I-77 exit 83 |
| North Carolina | Surry | Elkin | 91.3 | 146.9 | | NC 268 Byp. to I-77 north – Elkin | Interchange; to Elkin Municipal Airport; I-77 exit 85 |
| North Carolina | Surry | Elkin | 92.8 | 149.3 | | US 21 Bus. south – Elkin | Northern terminus of US 21 Bus. |
| North Carolina | Wilkes | No major junctions | No major junctions | No major junctions | No major junctions | No major junctions | No major junctions | No major junctions | No major junctions |
| North Carolina | Alleghany | ​ | 111.2 | 179.0 | | Blue Ridge Parkway | Interchange via connector roads |
| North Carolina | Alleghany | Sparta | 118.2 | 190.2 | | NC 18 (Whitehead Street) – Laurel Springs | |
| North Carolina | Alleghany | Twin Oaks | 121.1 | 194.9 | | US 221 south – Jefferson | Southern end of US 221 concurrency |
| | | | 124.30.00 | 200.00.00 | | North Carolina–Virginia line | North Carolina–Virginia line |
| Virginia | Grayson | Independence | 3.86 | 6.21 | | US 221 north / US 58 (Main Street) – Mouth of Wilson, Galax | Northern end of US 221 concurrency |
| Virginia | Grayson | Elk Creek | 14.77 | 23.77 | | SR 658 (Comers Rock Road) – Comers Rock | |
| Virginia | Grayson | ​ | 15.67 | 25.22 | | SR 805 (Spring Valley Road) to SR 94 – Fries | |
| Virginia | Wythe | Speedwell | 21.26 | 34.21 | | SR 619 (Saint Peters Road) / SR 749 (Cedar Springs Road) – Cedar Springs, Rural Retreat | |
| Virginia | Wythe | ​ | 26.03 | 41.89 | | SR 690 (Crockett Road, Cripple Creek Road) – Crockett, Cripple Creek | |
| Virginia | Wythe | ​ | 31.13 | 50.10 | | SR 696 (Barrett Mill Road) – Big Survey Wildlife Management Area | |
| Virginia | Wythe | Wytheville | 33.63 | 54.12 | | US 11 south (Lee Highway) | Southern end of US 11 concurrency |
| Virginia | Wythe | Wytheville | 33.94 | 54.62 | | US 11 north (Main Street) | Northern end of US 11 concurrency |
| Virginia | Wythe | Wytheville | 34.99 | 56.31 | | I-81 / US 52 to I-77 – Bristol, Roanoke | Northern terminus; I-81 exit 70; road continues west as US 52 (4th Street north) |
| 1.000 mi = 1.609 km; 1.000 km = 0.621 mi Concurrency terminus HOV only Incomplete access ||||||||

## Special routes and auxiliary routes

There are currently four business loops, four connectors, and one truck route along its route.
* U.S. Route 21 Business (Beaufort, South Carolina)
* U.S. Route 21 Business (Orangeburg, South Carolina)
* U.S. Route 21 Connector (Orangeburg, South Carolina)
* U.S. Route 21 Connector (West Columbia, South Carolina)
* U.S. Route 21 Connector (Columbia, South Carolina)
* U.S. Route 21 Connector (Ridgeway, South Carolina)
* U.S. Route 21 Business (Fort Mill, South Carolina)
* U.S. Route 21 Business (Elkin, North Carolina)
* U.S. Route 21 Truck (Sparta, North Carolina)
Auxiliary routes of US 21:
* U.S. Route 121
* U.S. Route 221
* U.S. Route 321
* U.S. Route 421
* U.S. Route 521