NC 16 is part of a three-state route 16 that connects the Charlotte region with northwestern West Virginia.

NC 16 is part of a three-state highway 16, that totals 475 miles (764 km), from Waxhaw, North Carolina to St. Marys, West Virginia.

Going counter-clockwise around Uptown Charlotte, John Belk Freeway becomes Brookshire Freeway (with US 74 leaving to follow Independence Boulevard out of the city); at the I-77/US 21 interchange (exit 5/exit 11), NC 16's concurrency with I-277 ends and the highway becomes Brookshire Boulevard.

In the Paw Creek neighborhood, NC 16 connects again with I-485 (exit 16) before leaving the Charlotte city limits.

Crossing Rozzelles Ferry Bridge at Mountain Island Lake/Catawba River, NC 16 enters Gaston County.

NC 16 through Gaston, Lincoln and southeast Catawba County is a four-lane expressway, with superstreet design at some at-grade intersections.

Continuing north, the highway meanders through the Brushy Mountains, entering Wilkes County at Kilby Gap (1,657 feet (505 m)).

In a northwesterly direction, NC 16 travels through Millers Creek and Wilbar before ascending along Piney Ridge and entering Ashe County at Horse Gap (3,110 feet (950 m), highest point along route).

[7][8] Immediately entering Ashe County is the Blue Ridge Parkway followed by NC 163 towards West Jefferson.

In 1940, NC 16 was rerouted to its current northern terminus at the Virginia state line, in Grassy Creek, with continuation as SR 92 to Mouth of Wilson.

Its old alignment to North Wilkesboro continued on as NC 18; while Boone Trail (SR 1500), to Cricket, was downgraded.

[15] In 1958, NC 16 was placed on new primary road west from its former alignment, Old North Carolina Highway 16 (SR 1573), bypassing Crumpler and Grassy Creek.

[11] In 1931, Virginia established SR 139 to connect with NC 681 at the state line, which continued to Mouth of Wilson.

NC 16 Business also connects the communities of Triangle and Westport, along the western banks of Lake Norman.