NC 81 was designated in 1934 as a renumbering of NC 10 from US 25 to US 70/US 74. The road was then extended in 1937 when US 25 was rerouted in Asheville. NC 81 was placed south along Biltmore Avenue to the current end of the road at the intersection of US 25 and US 25A. Then in 1938 the road was extended to its current terminus at US 70.