It runs 355 miles (571 km) from Buena Vista, Virginia at U.S. Route 60 to Myrtle Beach, South Carolina at U.S. Route 17 Business.
U.S. Route 66 | U.S. Route 1 | 501(c)(3) | U.S. Route 6 | U.S. Route 101 | Route 66 | U.S. Route 30 | New Jersey Route 4 | European route E65 | U.S. Route 40 | California State Route 1 | U.S. Route 1 in Maine | Pennsylvania Route 309 | European route E18 | U.S. Route 23 | European route E4 | U.S. Route 9 in New York | U.S. Route 11 | Pennsylvania Route 82 | European route E70 | U.S. Route 90 | U.S. Route 75 | U.S. Route 61 | U.S. Route 60 | Pennsylvania Route 73 | New York State Route 32 | European route E55 | U.S. Route 80 | U.S. Route 71 | U.S. Route 51 |
The business routes and US 221 pass through a commercial area and by the Anne Spencer House, then turn west onto 12th Street and cross Norfolk Southern's Danville District rail line a few blocks south of the Lynchburg-Kemper Street Station, which is served by Amtrak.
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The rest of the road runs straight through rural forestland until it approaches the Waccamaw River Memorial Bridge (Main Street Bridge) over the Waccamaw River and after crossing the bridge enters Conway Downtown Historic District.
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North of 4th Avenue US Bus 501/701 passes by more historic sites in the city such as the City Post Office, the Beaty-Little House, the Burroughs School and others.