U.S. Route 601 (US 601) is a north–south United States highway that runs for 316.3 miles (509.0 km) from U.S. Route 321, near Tarboro, South Carolina, to U.S. Route 52, in Mount Airy, North Carolina. In North Carolina, it is one of the main north-south corridors connecting the cities of Salisbury, Mocksville, and Mount Airy.

U.S. Route 321 (US 321) is a spur of U.S. Route 21. It runs for 516.9 miles (831.9 km) from Hardeeville, South Carolina to Lenoir City, Tennessee; with both serving as southern termini. It reaches its northernmost point at Elizabethton, Tennessee, just northeast of Johnson City. Because of its unusual "north–south–north" routing, U.S. Route 321 intersects both Interstate 40 and U.S. Route 70 three separate times. The highway serves different roles in each state: An alternate route to interstates in South Carolina, a major highway in North Carolina, and a scenic route in Tennessee.