State Route 64 is an east–west route in Lauderdale County in the northwest portion of the state. The western terminus of the route is at its junction with U.S. Highway 43 near Green Hill, an unincorporated community south of the Alabama-Tennessee state line. The eastern terminus of the route is at its intersection with State Route 207 north of Anderson.

State Route 64 travels 18 miles (29 km) along a two-lane roadway as it passes through northern Lauderdale County. The route connects the small towns of Anderson and Lexington with US-43, which leads southward into Florence and Muscle Shoals.

The entire route is in Lauderdale County.