Ohio State Route 321 is a short east-west route in southern Highland County, in southwestern Ohio. It serves the small town of Mowrystown. The western end of Ohio Route 321 is found along Ohio Route 134, just short of that route's fork with Ohio Route 138. This is at the unincorporated community of Buford. Ohio Route 321 runs southeasterly from there to Mowrystown, where the route bends northeasterly. This gives Ohio Route 321 a sort of "V"-shape. Ohio Route 321 continues northeast for just a couple of miles before ending at US Route 62.