Wyoming Highway 451 is a 5.026-mile (8.1 km) east-west Wyoming State Road in Weston County that acts as a spur from U.S. Route 16 at Osage west to Weston County Routes 22 and 36B.

Wyoming Highway 451 begins its western end west of Osage at Weston County Route 22 and County Route 36B just west of Beaver Creek in the Thunder Basin National Grassland. County Route 22 (Oil City Road) is the continuation of the roadway westward. WYO 451 heads west and ends at US 16 in the Census-designated Place (CDP) of Osage.

The entire route is in Weston County.