At 12.58 miles (20.25 km) long, the highway runs from the West Virginia state line at the New Martinsville Bridge near Hannibal to SR 78 in Adams Township.

The route south of the northernmost intersection with SR 7 in Hannibal is not signed by the Ohio Department of Transportation (ODOT).

SR 536 begins unsigned at the West Virginia state line on the New Martinsville Bridge while crossing over the Ohio River.

The route heads due west over the remainder of the bridge until both directions of the two-lane road split apart and immediately intersect SR 7, a divided highway.

Except when it descends into the Opossum Creek valley, it remains at the top of the hills as it travels northwest through Ohio and Green Townships as well as portions of the Wayne National Forest.