The western terminus of State Route 151 is at a T-intersection with U.S. Route 250 approximately 5 miles (8.0 km) southwest of Bowerston.

Its eastern terminus is at a diamond interchange with State Route 7 just south of Mingo Junction.

State Route 151 travels through Harrison and Jefferson Counties.

Only the segment of SR 151 that is concurrent with US 22 near Hopedale is included within the National Highway System.

[2] When it was first established in 1924, State Route 151 consisted of what is now a stretch of State Route 212 between Sherrodsville and Bowerston and the current portion of State Route 151 between Bowerston and its current eastern terminus at State Route 7 near Mingo Junction.