US 501 in South Carolina is a north–south United States highway that traverses 73.8 miles (118.8 km); it is one of main routes to the Grand Strand.

From Myrtle Beach to Marion, US 501 is a multilane highway, some sections divided, some undivided, mostly with at-grade intersections but having a number of interchanges along the length.

US 501 is a north–south United States highway that traverses the majority of North Carolina in concurrency with US 15, known as "15-501" ("Fifteen Five-o-one").

[2] Merging with US 15, it becomes what is known by local residents as "15-501" ("Fifteen Five-o-one"), a concurrency that extends for 106 miles (171 km) across central North Carolina.

[2] After Durham, US 501 goes north to Roxboro, then into South Boston, Virginia after crossing the state line; the majority of this section is a four-lane expressway.

[3][5] US 501 continues through South Boston on Wilborn Avenue, a five-lane road with center turn lane.

US 501 receives the northern end of SR 129 (Old Halifax Road) shortly before leaving the town of South Boston.

The U.S. Highway enters the town of Halifax and becomes Main Street, a three-lane road with center turn lane, at its grade crossing of Norfolk Southern's Durham District.

[3][5] US 501 passes through Volens and Acorn on its way to the hamlet of North Halifax, where the highway begins to run concurrently with SR 40 (Stage Coach Road).

The highways cross the Roanoke River into the town of Brookneal in Campbell County and pass under Norfolk Southern's Altavista District rail line.

[3][5] US 501 runs concurrently with US 29 and US 460 southwest along the northern slope of Candlers Mountain to a full Y interchange where US 501 heads northwest from the freeway.

SR 128 joins US 501 on Candlers Mountain Road between the intersection and the highway's cloverleaf interchange with US 29 Business (Lynchburg Expressway).

[3][5] US 501 heads northwest on two-lane Boonsboro Road, which becomes Lee Jackson Highway when it exits the city of Lynchburg into Bedford County.

The U.S. Highway curvaceously crosses Fleming Mountain and descends into the James River Gorge at Coleman Falls.

North of Big Island, the U.S. Highway crosses the river and immediately intersects SR 130 (Elon Road) on the Amherst County side.

The two highways have a curvaceous crossing of the spine of the Blue Ridge Mountains before descending to the town of Glasgow at the mouth of the Maury River.

South of the downtown area, US 501 veers onto Sycamore Street while US 501 Business continues along Magnolia Avenue.

In 2021, the South Carolina Department of Transportation and Horry County announced plans to spend tens of millions of dollars expanding U.S. 501 into four lanes each way near Myrtle Beach.

By 1926 the routing of NC 13 was shifted slightly to the west between Timberlake and Roxboro, providing a direct link between the cities.