The highway travels from Soperton north and northwest to Wrightsville, then turning northeast to Wadley and, finally, east, to its eastern terminus, at a point northwest of Midville.

It heads south, southwest, and northwest to an intersection with U.S. Route 221 (US 221)/SR 15/SR 56 in downtown Soperton.

North of Soperton, SR 78 has an interchange with Interstate 16 (I-16).

Just south of the town, they intersect SR 242.

East of the city, SR 78 meets its northern terminus, at an intersection with SR 17 northwest of Midville[1] The only portion of SR 78 that is part of the National Highway System, a system of routes determined to be the most important for the nation's economy, mobility, and defense, is the concurrency with SR 15 from Soperton to Wrightsville.