In the U.S. state of Ohio, Interstate 90 runs east–west across the northern tier. Much of it is along the Ohio Turnpike, but sections outside the turnpike pass through Cleveland and northeast into Pennsylvania.

In the western half of Ohio, Interstate 90 is jointly signed with the Ohio Turnpike/Interstate 80. Originally, I-90 was planned to be a separate road through Toledo, running parallel to the Ohio Turnpike.[citation needed] Parts of that route were built, and initially labeled State Route 2 until I-90 was complete to Toledo. However, the plan to build a separate road was abandoned, and the Ohio Turnpike–I-90 connector (designated Exit 8A, now Exit 142) was built in Lorain County in Amherst Township and Elyria Township by 1976.

From the exit east, I-90/State Route 2 travels east along the south shore of Lake Erie through Cuyahoga County to downtown Cleveland. State Route 2 separates from Interstate 90 at Detroit Road in Rocky River. Interstate 90 crosses the Cuyahoga River via the Innerbelt Bridge into downtown Cleveland and, after passing Dead Man's Curve, follows the East Shoreway northeastward along the lakeshore toward Euclid, again co-signed with State Route 2. Interstate 90 separates from State Route 2 in Euclid and passes through Lake County and Ashtabula County as it continues to travel northeast towards the Pennsylvania state line in Conneaut.

US 20 parallels Interstate 90 throughout Ohio, as it does in all locations from Illinois eastward; US 6 also parallels I-90 to a lesser extent throughout the state. East of Interstate 271, State Routes 84 and 307 also closely parallel I-90. These routes are usually easily accessible from I-90's interchanges.

The entire free section of I-90 in Ohio is called the "AMVETS Highway". Selected stretches are named for various individuals.

In Greater Cleveland, portions of I-90 carry various names, such as the Innerbelt Freeway, the Cleveland Memorial Shoreway, the Lakeland Freeway, and the Euclid Spur.