SR 49 continues north from US 35 through Trotwood along a roadway locally called the "Northwest Connector" or the "Trotwood Connector", then turns onto Salem Avenue, which crosses into Clayton. The route then briefly travels through Englewood, straddles the Englewood-Clayton line, again crosses into Clayton, then the ramps to and from Interstate 70 cross into Englewood and back into Clayton. SR 49 is then concurrent with I-70 for approximately through Clayton. SR 49 then exits from I-70 at ramps passing from Clayton into Clay Township, Montgomery County. The route then continues north to Greenville, Fort Recovery, Willshire, Convoy, Payne, Antwerp, Hicksville, Edgerton and Edon. SR 49 then interchanges with the Ohio Turnpike at that highway's first interchange east of the Indiana-Ohio state line. SR 49 terminates at the Ohio-Michigan state line where it continues north as Michigan State Highway 49.