^US 40 is joined by US 22 eastward into Cambridge, March 2021.
In Ohio, US Route 40 runs east-west across the middle of the state, alongside Interstate 70. Most of the time, US Route 40 is a two-lane highway; Interstate 70 does the heavy lifting along this corridor. It enters Ohio from Richmond, Indiana, and it leaves Ohio into Wheeling, West Virginia. In western Ohio, US Route 40 stays to the north of Dayton, just like Interstate 70, but it passes through some northern suburbs like Englewood and Vandalia. Next, US Route 40 goes right through downtown Springfield. Later on, US Route 40 passes north of London, but runs right through downtown Columbus. Beyond Columbus, US Route 40 goes through Reynoldsburg and other eastern suburbs before emerging into rural areas. It passes through a lot of small towns east of Columbus before reaching Zanesville and Cambridge. The next town after Cambridge served by US Route 40 is Old Washington, where US Route 40 joins Interstate 70 east for a while. Near Morristown, US Route 40 splits from Interstate 70, for the two routes to become a tag team again. US Route 40 winds through St. Clairsville as a two-lane highway, then it reaches Bridgeport. US Route 40 leaves Ohio by crossing a bridge over the Ohio River, from Bridgeport, Ohio to Wheeling, West Virginia.