US 340 was one of the original state roads designated by the Maryland State Roads Commission. The state road was constructed from Frederick to Knoxville in the early 1910s and completed to Harpers Ferry in 1919. The highway was designated Maryland's portion of US 340 in 1926. US 340 originally crossed the Potomac River at Harpers Ferry; however, the U.S. highway's bridge was destroyed by a flood in 1936. The modern US 340 Bridge was constructed at Sandy Hook between 1940 and 1947, with a long interruption due to World War II. The U.S. highway's freeway between Weverton and Frederick was constructed in the 1960s. Old sections of US 340 became part of Maryland Route 180 (MD 180).