United States Numbered Highways

The United States Numbered Highways (also known as U.S. Highways) is a national system of roads in the United States. These roads connect to places across the country. Some of the roads are freeways, which means cars must use ramps in order to get on or off the road, but others are surface roads. Many U.S. Highways, such as U.S. Route 66, have had their numbers removed because of the creation  of the Interstate Highway System.California Highways and Public Works, March-April 1964, Route Renumbering (PDF)

Numbering
U.S. highways have a special way to figure out their numbers. The main U.S. Highways usually have numbers with 1 or 2 digits. An exception is U.S. Route 101, which is a 3-digit route that is treated like a 2-digit route with a first digit of "10". U.S. Highways that run east/west are even numbers (2, 4, 6, 8, or 0), and north/south U.S. Highways are odd numbers (1, 3, 5, 7, or 9). For east/west U.S. Highways, the small numbers are in the north and the big numbers are in the south. For north/south U.S. Highways, the small numbers are in the east and the big numbers are in the west. The important east/west U.S. Highways usually have numbers ending in "0" and the important north/south U.S. Highways have numbers ending in "1". Many of the routes ending in "0" or "1" used to go across the country, but no longer do because of the Interstate Highway System.McNichol, Dan. The Roads that Built America:  The Incredible Story of the U.S. Interstate System. New York: Sterling Publishing Co., Inc., 2006. 

Examples
U.S. Route 20 is an important east/west U.S. Highway in the north part of the United States from Newport, Oregon to Boston, Massachusetts
U.S. Route 90 is an important east/west U.S. Highway in the south part of the United States from Van Horn, Texas to Jacksonville Beach, Florida
U.S. Route 1 is an important north/south U.S. Highway along the east end of the United States from Key West, Florida to Fort Kent, Maine
U.S. Route 101 is an important north/south U.S. Highway along the west end of the United States from Los Angeles, California to Olympia, Washington

Three-digit U.S. Highways
U.S. Highways that have 3-digit numbers are spurs of a 1 or 2 digit highway. For example, U.S. Route 201 is a spur of U.S. Route 1.

Exceptions
U.S. Route 2 is considered a major U.S. Highway even though it does not end in "0". U.S. Route 163, U.S. Route 400, U.S. Route 412, and U.S. Route 425 have 3-digit numbers that do not act as a spur of a 1 or 2 digit route.

Route 20 is an important east/west U.S. Highway in the north part of the United States from Newport, Oregon to Boston, Massachusetts U.S. Route 90 is an important east/west U.S. Highway in the south part of the United States from Van Horn, Texas to Jacksonville Beach, Florida The Dwight D. Eisenhower National System of Interstate and Defense Highways, commonly known as the Interstate Highway System, is a network of controlled-access highways that forms part of the National Highway System in the United States. The system extends throughout the contiguous United States and has routes in Hawaii, Alaska, and Puerto Rico.

 References 

Other websites

AASHTO Special Committee on U.S. Route Numbering
U.S. Numbered Highways - 1989 Edition  (AASHTO)
Highway History - Other Articles (Federal Highway Administration)
U.S. Highways: From US 1 to (US 830) 
US Highway Ends: maps and terminus photos