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 52 (US 52) is a north–south United States highway that runs for 150 miles (240 km) from the South Carolina state line, near McFarlan, to the Virginia state line, near Mount Airy. It serves as a strategic highway through the central North Carolina Piedmont. Because of its alignment in the state, US 52 does not follow the standard convention of an even U.S. route number going east–west.