State Route 331 is an east–west state highway in the eastern portion of the U.S. state of Ohio. State Route 331 has its western terminus at U.S. Route 22 approximately 4 miles (6.4 km) northwest of the village of Holloway. Its eastern terminus is at a signalized intersection with U.S. Route 40 nearly 2.75 miles (4.43 km) west of Saint Clairsville, and immediately south of Exit 213 off of Interstate 70.