U.S. Route 401 is a north–south United States highway, a spur of U.S. Route 1, that traverses along the fall line from Sumter, South Carolina to Interstate 85 near Wise, North Carolina.

Starting in Sumter, South Carolina, US 401 goes northeast through mostly swamp and farmland, as it connect the cities of Darlington and Bennettsville before crossing the state line into North Carolina. Traversing the state for 77.2 miles (124.2 km), it is mostly a two-lane rural road, which is likely to only have local traffic along it thanks to nearby Interstate 95.

In North Carolina, the highway becomes more utilized, as it connect to several mid-size and large cities in the state. In the sandhills region, it connects the cities of Laurinburg, Raeford, and Fayetteville. All three of which have business routes connecting the downtown areas. The road is typically two-lane still, but expands to four-lane (or more) in each city. The road takes a pause in the lime-light as it straddles nearby Interstate 95 again; from Fayetteville, through Lillington, to Fuquay-Varina.

In Wake County, US 401 is center-stage again as a major north-south corridor, connecting bedroom communities to downtown Raleigh. Once it leaves the county, it reverts to a rural road connecting the small cities of Louisburg and Warrenton. US 401 finally ends at Interstate 85, just north from the community of Wise; competing a 173.8-mile (279.7 km) thru the state.

Overall, the route goes through endless fields of farmland broken now and then by cities and small towns. With exceptions to both the sandhills region and Wake County, most travelers would be better served using Interstate 95.

The route is the third highway to bear the name, which included renaming the stretch of U.S. Route 15A from Sumter to Raleigh, and former N.C. Highway 59 from Raleigh to Norlina.

The first U.S. 401 was assigned to a route from South Hill to South Boston in Virginia from 1926 to 1932. Parts of this route were renumbered as U.S. Route 58. The second U.S. 401 ran from Raleigh to Waterboro in North Carolina from 1933 to 1934. Parts of this route were replaced by U.S. Route 15.

Prior to 2001, current U.S. 401 ran 257 miles (414 km) from Norlina, North Carolina at U.S. Route 1 to Sumter, South Carolina at U.S. Route 76 Business.

Considered an important link between Fayetteville, Lillington and Raleigh, NCDOT has set up the US 401 Corridor Study. The purpose of the study is to identify deficiencies in the existing corridor and develop alternatives for accommodating future growth in traffic volumes (i.e. widen to multi-lanes). The corridor study also includes NC 55 and NC 210. Estimated costs for all road improvements along the corridor is around $193–222.6 million. Property acquisition and construction is unfunded at this time.

Established in 1958, when mainline US 401 was bypassed south of Bennettsville, it followed the old alignment via Main Street and Tyson Avenue. By 1990, the route was decommissioned with most being replaced by an extension of SC 385.

Established in 1957, when US 401 was re-established, it replaced US 15A alignment through downtown Laurinburg, via Main Street. It was renumbered in 1960 into US 401 Business.

Established in 1960 as a renumbering of US 401A through downtown Laurinburg, it has remained unchanged since.

The entire route is in Laurinburg, Scotland County.

In 1954, US 15A was rerouted onto a bypass around Raeford, the old alignment through downtown was unnumbered until around the early 1960s, when it became US 401 Business. The route follows Harris Avenue, Main Street, and Central Avenue.

The entire route is in Raeford, Hoke County.

Established in late 1960s from a renumbering of US 401, this business loop goes through Fayetteville via Raeford Road, Robeson Street, Martin Luther King Jr Freeway, and Ramsey Street.

The entire route is in Fayetteville, Cumberland County.