State Route 22 is a 168.5-mile (271.2 km) state highway that extends from Safford in Dallas County to the Georgia state line near Roanoke in Randolph County. The route runs across most of the state from west to east.

Starting at a junction with SR-5 in Safford, the route runs northeast through Selma and Maplesville. At Clanton the highway is co-routed for eight miles (13 km) with U.S. Highway 31, including an intersection with Interstate 65 near the geographical center of the state. The route proceeds towards Verbena and then crosses Mitchell Lake.

The route continues east-northeast through Rockford, Alexander City, New Site and Roanoke on its way to the Georgia border, where the road becomes State Route 34. The route is paved throughout and occasionally multi-lane. Counties traversed by the route include Dallas, Chilton, Coosa, Tallapoosa, Chambers, and Randolph.