State Route 49 is a 82.7-mile (133.1 km) long state route in the central and eastern part of the state. The southern terminus of the route is at an interchange with Interstate 85 at Franklin in Macon County. The northern terminus of the route is at its junction with State Route 281 east of Cheaha State Park in southern Cleburne County.

State Route 49 serves a connecting route giving access to several major routes for residents of rural areas and small towns along its route. For motorists in Macon County, it serves as an access route to Interstate 85 leading towards Montgomery. Motorists in southern Tallapoosa County use State Route 49 to access U.S. Highway 280 leading towards Alexander City and Birmingham; the two routes intersect at Dadeville. North of Dadeville, State Route 49 passes through rural areas and small towns in eastern Alabama, passing through New Site, Mellow Valley and Lineville.

When State Route 49 was created in 1940, the route ran only from Tallassee to Dadeville. As a result of several northward extensions, by 1969 the route extended to a junction with U.S. Highway 78 near Heflin. In 1973, the route was extended southward to its current terminus at Interstate 85 in Macon County. When State Route 281 was created in 1995, the northernmost section of the route was truncated.