Established in the mid-1920s, SR 216 traverses heavily wooded terrain as it connects the villages of Murray City and New Straitsville.

When it first appeared, SR 216 extended south to Nelsonville and north and east to Shawnee and Corning.

[2] The state highway begins at a three-way stop T-intersection with SR 78 in the village of Murray City, just west of the Hocking-Athens County Line.

Known as Locust Street, SR 216 runs northerly a short distance through a residential area before departing the village, and entering into rural Ward Township.

Turning to the northwest inside of the village limits, SR 216, which is also known as Main Street, passes a blend of woods and homes.