The Cumberland Gap was the chief passageway through the Appalachian Mountains in early American history. It was formed as an ancient creek, flowing southward, cut through the land being pushed up to form the mountains. As the land rose even more, the creek reversed direction flowing into the Cumberland River to the north. Used in prehistoric times by migrating animal herds, the Indians used it after their arrival into North America. The gap was named for Prince William Augustus, Duke of Cumberland who sponsored an expedition into the area in 1750. In 1775, Daniel Boone brought a company of men to cut out a path through the gap to enable a settlement effort by the Transylvania Company in Transylvania. The trail was widened in the 1890s to accommodate wagon traffic. It is estimated that between 200,000 and 300,000 immigrants passed through the gap on their way into Kentucky and the Ohio Valley before 1810. U.S. Highway 25E passed through the gap before the completion of a tunnel in 1996.

See Cumberland Gap (A74 road) for a section of road in the U.K.