US 1 runs northeast, passing through or closely bypassing Southern Pines and Sanford in the Sandhills region.

Passing Rockingham Speedway, the road widens to a divided expressway (two lanes in each direction) and meets the northern end of North Carolina Highway 177 (NC 177).

After passing through the town of Hoffman as a five-lane boulevard with a center turn lane, US 1 enters Moore County.

US 1 follows a partially controlled-access expressway though Southern Pines, bypassing the downtown area.

After North May Street, it becomes a brief four-lane arterial before returning to a partially controlled-access expressway after Aiken Road.

Outside of Sanford, US 1/US 15/US 501 briefly run concurrent with NC 87 and then intersect US 421, which provides access to Lillington and Wilmington southbound and Greensboro and Winston-Salem northbound.

Passing between Apex to the north and Holly Springs to the south, the route has an interchange with NC 540 (Triangle Expressway) and merges with US 64 as it crosses into Cary.

At the Raleigh–Cary line, near the Crossroads Plaza shopping center, it has an interchange with I-40 and begins an 11-mile (18 km) concurrency with I-440 along the Raleigh Beltline.

US 401 leaves US 1 to follow Louisburg Road, and US 1 continues past the Triangle Town Center shopping mall and I-540.

The section from I-440 to I-540 is mostly six lanes wide with a median though with numerous business entrances and cross streets.

Upon entering Vance County, US 1 passes through the small town of Kittrell and becomes a freeway bypass around the city of Henderson, with US 1 Bus.

There is a second interchange with I-85 near Middleburg, before US 1 enters Warren County, and, in the town of Norlina, US 158 leaves US 1, while US 401 joins it for a second time.

US 1 turns from the northeast to a more northerly route, passes through the community of Wise, and has a third interchange with I-85 where US 401 has its northern terminus.

[6] It differed from US 1 north of Norlina, where it ran via Emporia, Virginia, and Roanoke Rapids and between Southern Pines and Rockingham, where a route via Pinehurst—where the association's president lived—was followed.

[11][12] In 1922, the route was designated as NC 50, from the South Carolina state line to Roanoke Rapids.

[13][14][failed verification] In 1999, the North Carolina Department of Transportation (NCDOT) submitted a request to the American Association of State Highway and Transportation Officials (AASHTO) to designate 32.36 miles (52.08 km) of US 1 from I-40, in Raleigh, to the future US 421 (Sanford Bypass) interchange, in Sanford as I-140.

In June 2005, a new freeway bypass was built east of Vass and Cameron; the old route became US 1 Bus.

From I-540 to I-440 (the Capital Boulevard section in Raleigh) it is recommended be improved to an expressway (nearby freeway I-540 will maintain mobility).

[18] The Strategic Corridors Initiative is an effort to protect and maximize mobility and connectivity on a core set of highway corridors, while promoting environmental stewardship through maximizing the use of existing facilities to the extent possible, and fostering economic prosperity through the quick and efficient movement of people and goods.

[26] State law calls on each municipality to work cooperatively with NCDOT to develop such a plan to serve present and future travel demand.

[27] In November 2011, seven public charrettes were held to document local priorities on five transportation areas within the county, including US 1.

[30] The strongest opposition of any type of US 1 improvement has come from some area residents, the equestrian community, and some business leaders.

[31] At this time, the cooperative effort to develop a Comprehensive Transportation Plan for Moore County is continuing.

The widening project from the Moore County line to near NC 177 has been recently completed from a two-lane principal highway to mostly a five-lane road with a small divided section near the Mackall Airfield.