The highway travels concurrently with South Carolina Highway 4 (SC 4) on Stonewall Jackson Boulevard, then with US 21/US 178 on Joe S. Jeffords Highway/Whittaker Parkway/Chestnut Street.

The highway is in complete concurrency with US 521 Truck on Springdale Drive and Boykin Road.

is a business route of US 601 that follows the original mainline of US 601 along Hampton Street.

U.S. Route 601 Business, established in 1970, is a 4.1-mile (6.6 km) business loop that follows the original mainline route through downtown Dobson, via Main Street.

U.S. Route 601 Business was established in October 1965 and followed the original route through downtown Concord, via Church and Union Streets and in concurrency with NC 73.