State Route 81 is an east–west route in western Ohio. Its western terminus is at the Indiana state line near Willshire (the route continues as State Road 124), and its eastern terminus is at State Route 53 in Patterson. The route also goes through or close to the towns of Elgin, Lima, Ada, and Dunkirk.

State Route 81 was certified in 1926. It was originally routed from Ada to Patterson on a former eastern heading of the now-defunct State Route 69, which was rerouted to Mount Cory (this route is now part of State Route 235). It was extended to the Indiana state line in 1940 along formerly unnumbered roads from Ada to Lima and along the route of the now-defunct State Route 704 from Lima to the state line.

Before 1926, State Route 81 was a short route in northeastern Ohio. In 1926, its route became part of State Route 82.