The state route begins at a
diamond interchange with the US 24 freeway (exit 28). The interchange is partially within the city limits of Defiance and partially in
Richland Township. Defiance County Route 175 heads north from the interchange while SR 281 heads south along Domersville Road often crossing between Defiance and Richland Township. After a traffic signal at a connector road to Defiance County Route 424, the route crosses the
Maumee River on a
plate girder bridge. A short distance later, SR 281 intersects
SR 18 and the two routes form a
concurrency and head east out of the city past a
General Motors factory. After , the SR 18 concurrency ends and SR 281 continues due east. Outside of the Defiance area, the route's surroundings becomes much more agricultural. After exiting
Defiance County, it enters
Henry County. SR 281 does not pass through any incorporated villages through Henry County, but it intersects
State Routes 108,
109, and
65. After crossing into
Wood County, SR 281 enters the small village of
Custar. SR 281 continues east intersecting
SR 235 and
SR 25 but also passes over
Interstate 75 without an interchange. After its intersection with
SR 199, SR 281 turns to the northeast and enters the village of
Wayne. Through Wayne, the route has the road names of Main Street and Church Street. northeast of Wayne, SR 281 then passes through the village of Bradner first on Church Street, then due north on Main Street. SR 281 ends at as stop-controlled intersection with US 6 about north of Bradner. ==History==