The route connects US 50 in the Knox Township, Vinton County community of Bolins Mills to SR 56 in Waterloo Township, Athens County.

It heads north through the Raccoon Creek valley occasionally acting as the border of the Zaleski State Forest.

After approximately 3.3 miles (5.3 km), the creek and SR 356 diverge as the road heads north at the bottom of narrow valleys.

The route descends back into valleys, intersecting the northern terminus of SR 681 and passing through the community of Mineral.

[2] The first segment of SR 356 brought into the state highway system was in 1932 as an unnumbered spur between SR 56 and the Waterloo State Forest, south of Mineral.