 The road follows Bluewater Highway along the river, passing to the north of Saranac. It turns northeasterly through lightly forested farmland passing Bertha Brock Park as it approaches the city of Ionia. In town, M-66 runs concurrently along M-21 for a few blocks in the central business district. Bluewater Highway leaves town and continues along the Grand River to Muir, and the trunkline crosses the Maple River on east side of town. M-21 follows the course of the Maple briefly before turning east through farms along the Stony Creek to Pewamo. The highway bypasses the village to the south and crosses into Clinton County near the eastern edge of town. Western Clinton County's landscape is dominated by farms, interrupted by the community of Fowler. The highway enters the county seat, St. Johns on State Street, passing through a residential section of town. In the middle of downtown, M-21 intersects 2nd Street, which carries Business US Highway 127 (Bus. US 127). East of downtown, M-21 passes back into agricultural land and under the US 127 freeway. The landscape is once again dominated by these farms through the western side of the county.
