The highway serves the cities of Lumberton, Fayetteville, Wilson, Rocky Mount, and Roanoke Rapids.

Traveling mostly northeasterly from the border, the freeway is joined in an overlap with US Highway 301 (US 301) at exit 10, and then I-95/US 301 intersects I-74 in Lumberton.

From there, I-95 turns due northward through a rural area of the state, past the small farming community of St. Pauls.

I-95 intersects I-40 in Benson, then runs along bridges over the Neuse River between Four Oaks and Smithfield, the latter of which contains a notable retail outlet complex.

The North Carolina Department of Transportation (NCDOT) operate and maintain two welcome centers and six rest areas along I-95.

[3] The North Carolina Department of Public Safety (NCDPS) operate and maintain four truck inspection/weigh stations along I-95.

[4] I-95 in North Carolina feature numerous dedicated or memorialized bridges, interchanges, and stretches of freeway.

Established in 1956, as part of the Federal-Aid Highway Act of 1956, I-95 was routed along or near existing US 301 throughout the state of North Carolina.

By 1961, two stretches of the Interstate opened: from mile marker 56, in Fayetteville, to milemarker 107, near Kenly; the other a small bypass near St. Pauls.

In 1964, the St. Pauls section extended further south into Lumberton; while another small stretch opened from US 158, in Roanoke Rapids, to the Virginia state line.

In 1969, I-95 was extended further south from Roanoke Rapids to exit 145, in Rocky Mount (later used for North Carolina Highway 4 [NC 4]).

Support has grown in a number of factors including the fact that the Interstate is mostly rural and used predominantly by out-of-state drivers.

[12] On January 20, 2012, NCDOT received final approval of the environmental assessment for improvements along I-95 in North Carolina.

Though the toll rates have not been established, a NCDOT report suggest charging $0.192 per mile ($0.119/km) for cars in the phase 1 section, with a much lower rate of $0.064 per mile ($0.040/km) on phase 2 sections; which would work out to be $19.20 from border to border (trucks with three axles or more will be charged more).