SR 106 begins at an intersection with US 29/SR 8 (General Daniels Avenue South), northeast of Athens, in southern Madison County. It travels northwest and curves to the north-northeast. It continues on this orientation to the town of Ila, where it intersects SR 98. Just northeast of town is the southern terminus of SR 174 SR 106 heads to the north and crosses the Hudson River into Franklin County. West of Sandy Cross, it meets SR 51 (Sandy Cross Road). Farther to the north is the eastern terminus of SR 326. The highway crosses the Middle Fork Broad River before entering Carnesville. In town, it intersects SR 59 (Commerce Road). The two highways run concurrent into the main part of town. There, SR 145 (Royston Road) joins the concurrency. SR 59 splits off to the northeast, while SR 106/SR 145 reach an interchange with Interstate 85 (I-85). Farther to the north, SR 106 departs the concurrency to the northwest. It continues its northwesterly jaunt and enters Stephens County. Less than 1 mile (1.6 km) after the county line are intersections with the northern terminus of SR 320 and SR 63 (Sunshine Road). Here, SR 63/SR 106 begin a concurrency to the north. Just before reaching Toccoa is SR 17, which serves as a bypass of the town. SR 63/SR 106 continue into Toccoa, until they meet their northern terminus, an intersection with US 123/SR 184/SR 365 (Currahee Street). At this intersection, not only do SR 63 and SR 106 both meet their northern terminus, but SR 184 turns to the north, onto Broad Street.
SR 106 is not part of the National Highway System, a system of roadways important to the nation's economy, defense, and mobility.