In North Carolina, US 258 connects Jacksonville with the Inner Banks communities of Kinston, Snow Hill, Farmville, Tarboro, and Murfreesboro.

The business routes head east together as Marine Boulevard toward downtown Jacksonville; US 17 Business heads southwest along Wilmington Highway to meet up with US 17 along the freeway bypass of Jacksonville that also carries NC 24 and leads to Marine Corps Base Camp Lejeune.

US 258 comes to a diamond interchange with I-587 and US 264 (John P. East Memorial Highway) and Wesley Chapel Road northeast of the center of Farmville.

US 258 joins the I-587 and US 264 freeway west for about three miles (4.8 km) before exiting at another diamond interchange northwest of town.

US 258 has a junction with NC 561 north of Scotland Neck; the two highways cross the Roanoke River into Northampton County.

The two highways meet the northern end of NC 308 just before entering Rich Square as Main Street.

The U.S. Highway joins US 158 east into Hertford County on its four-lane divided southern bypass of the town while the roadway continues straight as US 158 Business (Main Street).

[2][3] US 258 meets the western end of SR 189 (Quay Road) before reaching its diamond interchange with US 58 (Southampton Parkway) south of the independent city of Franklin.

US 258 joins US 58 on a four-lane freeway heading east while the roadway continues north into the city as US 258 Business (South Street).

US 258 and US 58 head southeast through a widely spaced partial cloverleaf interchange with SR 714 (Pretlow Street) before crossing the Blackwater River into the city of Suffolk.

When Great Mill Highway continues north toward an industrial area on the east side of Franklin, US 258 veers northeast on Camp Family Highway, crosses over Norfolk Southern Railway's Franklin District, and meets the northern end of US 258 Business at its intersection with US 58 Business (Carrsville Highway) just north of its grade crossing of CSX's Portsmouth Subdivision rail line and just south of Franklin Municipal-John Beverly Rose Airport.

[2][3] US 258 continues northeast as Walters Highway through the hamlet of Walters to the town of Windsor, where the highway is named Prince Boulevard, has a grade crossing of Norfolk Southern's Norfolk District rail line, and intersects US 460 (Windsor Boulevard).

US 17 turns north onto Jefferson Avenue while US 258 continues east on Mercury Boulevard into the city of Hampton.

East of SR 415 (Power Plant Parkway), US 258 meets Interstate 64 at an interchange featuring a pair of flyover ramps.

[2][3] US 258 crosses Newmarket Creek just west of the highway's partial cloverleaf interchange with La Salle Avenue.

The U.S. Highway reduces to six lanes at its diamond interchange with SR 278 (King Street), which serves Langley Air Force Base.

Ingalls Road continues south onto the former military base at Old Point Comfort that was decommissioned in September 2011.

US 258 Business begins at a diamond interchange with the US 58 freeway in Southampton County; the highway immediately enters the city of Franklin as South Street.

The business route passes to the south of the Franklin campus of Paul D. Camp Community College on its way to the downtown area.

Just west of the Blackwater River, US 258 Business curves north onto Main Street, which crosses over CSX's Portsmouth Subdivision rail line.

The two business routes exit the city of Franklin by crossing the Blackwater River into Isle of Wight County.

The highway runs 3.07 miles (4.94 km) between intersections with US 258 and SR 10 on the west and south sides of Smithfield.