SR 81 begins at an intersection with US 19/US 41/SR 3 (Bear Creek Boulevard), just north of Hampton, in Henry County.

From the downtown square to an intersection with SR 155 (Zack Hinton Parkway) the highways form an east–west one-way pair.

SR 81 then heads to the southeast before curving to the northeast and crosses over the South River, into Newton County.

The intersection with SR 162 is under construction to install a new roundabout; completion is expected in May 2020, with traffic opening in January 2020.

Immediately after leaving Porterdale, it enters Covington, where it turns north and intersects US 278/SR 12, before passing under, but not interchanging I-20.

[7] Just before entering Winder, the highway passes Fort Yargo State Park on its western end.