Wyoming Highway 387 begins its west end at I-25/US 87 (exit 227).

WYO 387 continues east entering the town of Edgerton just shortly after leaving Midwest.

At 19.3 miles (31.1 km) WYO 387 intersects the eastern terminus of Wyoming Highway 192 (Sussex Road).

At approximately 38 miles (61 km), WYO 387 intersects the southern terminus of Wyoming Highway 50 at Pine Tree Junction.

From there Highway 387 heads in a more northeasterly direction towards its east end.