NC 54 first appeared as an original state highway running from NC 75 in Pittsboro to Moncure. However, by 1928 the route was recommissioned as a secondary road which remains today as Moncure Pittsboro Road. The current NC 54 was signed in 1929 from Graham to US 70 south of Durham. In 1930 it was further extended through Rockingham to the Virginia border, however in 1940 much of that routing was renumbered as NC 87. The route was further extended in 1953 where it ran concurrent along US 70A until reaching US 1 in Cary. The Chapel Hill Bypass was completed in 1956 and NC 54 was rerouted from its downtown Chapel Hill routing to the new bypass. The last major change to the routing occurred in 1963 when NC 54 was extended along Hillsborough Street to the then-new US 1 freeway (present day I-440).