From NC 86's southern terminus at US 15/US 501/NC 54 Bypass (Fordham Boulevard) in Chapel Hill, the highway passes through the town's center and the campus of the University of North Carolina at Chapel Hill.

Exiting Chapel Hill, the highway intersects I-40 before crossing into rural Orange County.

After passing through central Yanceyville, US 158 splits west while NC 86 continues north to the state line, where the route continues as State Route 86 and travels into Danville, Virginia.

The highway was moved to the more heavily traveled corridor between Chapel Hill and Hillsborough in the 1950s.

The routing is well marked throughout and there are warning signs for truck drivers, including "tolerance ends," for that continue through the city.