In the initial 1918 state highway system, State Route 16 ran from State Route 2 (now U.S. Route 15) at Madison Mills to State Route 3 (now U.S. Route 11) at New Market via Madison and Luray, crossing the Blue Ridge Mountains at Fishers Gap. North of Madison, this was the path of the Blue Ridge Turnpike. In 1921, the State Highway Commission recommended that the legislature relocate SR 16 to run via Sperryville and Thornton Gap rather than Stanley to eliminate a very difficult and expensive crossing of the Blue Ridge and provide a direct connection with the Lee Highway at Sperryville. By 1923, SR 16 was truncated to Sperryville; the piece from Sperryville west to New Market became an extension of State Route 21.