State Route 281 (SR 281) is an east–west state highway in the northwestern portion of the U.S. state of Ohio. Its western terminus is at U.S. Route 24 approximately four miles (6.4 km) northeast of downtown Defiance, and its eastern terminus is at US 6 nearly one mile (1.6 km) north of Bradner. The majority of the route is known as the Defiance Pike.