State Route 721 (SR 721) is a north–south state highway located in the western portion of the U.S. state of Ohio. The southern terminus of SR 721 is at a T-intersection with SR 49 approximately 2.75 miles (4.43 km) south of the village of Potsdam. Its northern terminus is also at a T-intersection, this time with SR 185 on the Darke–Miami County Line nearly 1.50 miles (2.41 km) north of Bradford.