U.S. Route 50 runs east–west across the southern part of the state of Ohio, passing through Cincinnati, Chillicothe, and Athens. It is mainly a two-lane road except for the easternmost and westernmost parts. Near Athens it runs concurrently with State Route 32 (SR 32), a four-lane divided highway known as Corridor D, and from Coolville to the Ohio–West Virginia border it also overlaps SR 7 before crossing into Parkersburg, West Virginia.

State Route 32 (SR 32), also known as the James A. Rhodes Appalachian Highway, is a major east–west highway across the southern portion of the U.S. state of Ohio. It is the eighth longest state route in Ohio, spanning southern Ohio from Cincinnati to Belpre, across the Ohio River from Parkersburg, West Virginia. Except in Belpre, leading up to the bridge into West Virginia, the entire route outside Cincinnati's beltway is a high-speed four-lane divided highway, forming the Ohio portion of Corridor D of the Appalachian Development Highway System.