The southern section of State Highway 54 runs for just under ten miles (16 km),[1] entirely within Tillman County.

Midway through the route's extent, it passes through the town of Hollister, where it crosses a railroad track.

From this point, it heads due northward to pass the western terminus of State Highway 49.

It then runs along the western limit of Weatherford and continues 17 miles (27 km) north to end at State Highway 33 east of Thomas.

[4] The original path of the highway began at US-277 in Cyril and proceeded west, intersecting US-62 in Apache.

On the west side of Weatherford, the highway turned north along its current alignment.