Ohio State Route 281 is an east-west highway in northwestern Ohio. It parallels US Route 6 to the south, but its eastern extend curls north to end at US Route 6 near Bradner. Starting at that eastern end, Ohio Route 281 runs southwest through Radner. At Ohio Route 199, just after passing southwesterly through the town of Wayne, Ohio Route 281 straightens out into a due-west direction all the way to Defiance, where it ends. Ohio Route 281 turns northerly on the east side of Defiance to end at US Route 24.