SR 216 begins as secondary highway in Obion County at an intersection with US 45W/SR 5/SR 21.

The highway then winds its way southeast through farmland to cross into Weakley County.

[2] SR 216 becomes Mount Pelia Road as it passes through the community of Mount Pelia before winding its way eastward and entering Martin, where it passes through some neighborhoods before splitting off onto Baker Road.

It then becomes concurrent with SR 43 (Skyhawk Parkway) as they bypass downtown and come to an interchange with US 45E and US 45E Business (Elm Street/SR 372).

Prior to this point, the entire route of SR 216 is a two-lane highway.