State Route 220 is an east–west state highway in the south central portion of the U.S. state of Ohio. Its western terminus is at State Route 772 about 8¼ miles west of Waverly, and its eastern terminus is at the State Route 32/State Route 124 concurrency 3 miles (4.8 km) east of Piketon.

The entire route is in Pike County.

Recently, a Truck SR 220 has been added near Waverly so that trucks can bypass several turns in the downtown area while heading to and from U.S. Route 23. The route has two forks, one following Pride Drive for traffic heading to and from the north, and one following West 2nd Street for traffic heading to and from the south.