State Route 681 (SR 681) is a 39.53-mile (63.62 km) long east–west state highway in the southern portion of the U.S. state of Ohio. The western terminus of SR 681 is at a T-intersection with SR 356 approximately 6.75 miles (10.86 km) northwest of Albany. Its eastern terminus is also at a T-intersection, this time with SR 124 nearly 9.50 miles (15.29 km) southeast of Coolville.