State Route 49 (SR 49, Ohio 49) is a state highway in the western part of the U.S. state of Ohio. It begins at Drexel with US 35 and runs northwesterly to Greenville, and then runs roughly along near the western edge of the state near the Indiana state line to the Michigan state line where it meets with Michigan's M-49.

Route 49's southern terminus is west of Dayton, at the intersection of Williamson Street and 3rd Street. US 35 continues southward from this intersection as a limited-access expressway into downtown Dayton. Prior to 2000, State Route 49 followed Salem Avenue to a southern terminus in downtown Dayton.

Route 49 is concurrent with Interstate 70 for 1.5 miles between Dayton and Greenville.