States traversed: Ohio, West Virginia, and Virginia
US Route 250 is a northwest-southeast route from Sandusky, on the shores of Lake Erie in north-central Ohio, to Richmond, Virginia. US Route 250 doesn't really hit any major cities between its two endpoints, unless you consider Wheeling or Charlottesville to be major cities. The northern end of US Route 250 is at US Route 6 in Sandusky, Ohio. In Ohio, US Route 250 heads south from Sandusky to Ashland, New Philadelphia, and Bridgeport, which brings US Route 250 into Wheeling, West Virginia. From Wheeling, US Route 250 heads south to Fairmont, Elkins, and the Virginia border. In Virginia, US Route 250 proceeds east to Staunton, where Interstate 64 and US Route 250 follow the same corridor east toward Charlottesville and Richmond. The southeastern end in Richmond, Virginia, is where US Route 360 is interacting with a series of ramps to and from Interstate 95.