U.S. Route 250 (US 250) is a United States Numbered Highway that runs from Sandusky, Ohio, to Richmond, Virginia. Within the state of West Virginia, the route runs from the Ohio border in Wheeling to the Virginia border near Thornwood.

U.S. Route 50 in West Virginia runs from the border with Ohio to Virginia, passing briefly through Garrett County, Maryland, and following the Northwestern Turnpike. Prior to the U.S. Highway System it was West Virginia Route 1 and in the 1930s, the road was not finished in Maryland. Today the section of US 50 from Clarksburg to Parkersburg on the Ohio River is part of Corridor D of the Appalachian Development Highway System.