State Route 69 is a 280.6-mile (451.6 km) long route that extends from the southwestern to the northeastern parts of the state. The southern terminus of the route is at a junction with State Route 177 at Jackson. The northern terminus of the route is at its junction with U.S. Highway 431 and State Route 79 at Guntersville.

State Route 69 has a rather irregular trajectory for much of its route. From its origin at Jackson, the routes leads northwestwardly as it leads through Clarke County. In the northern part of the county, the route turns northeastward as it approaches Linden.

North of Linden, State Route 69 assumes a general northward trajectory, passing through Greensboro as it leads towards Tuscaloosa, the largest city the route passes through. At Tuscaloosa, State Route 69 is routed along Interstate 359 north of the junction of I-359 and Interstate 20/59. I-359 and State Route 69 share a wrong-way concurrency with U.S. Highway 11 as they lead into downtown Tuscaloosa.

North of Tuscaloosa and Northport, State Route 69 continues northward as it leads towards Jasper. At Jasper, State Route 69 and State Route 5 share a wrong-way concurrency along the former route of U.S. Highway 78.

North of Jasper, State Route 69 resumes its northeastward trajectory as it leads towards Cullman. South of Cullman, the route junctions Interstate 65 and shares a five-mile (8 km) long concurrency with the interstate route. State Route 69 is one of only two signed state routes that is co-routed along a stretch of interstate highway in Alabama. (State Route 5, along with U.S. Highway 11, are co-routed with Interstate 20/59 between West Blocton and Bessemer).

As State Route 69 leads northward from Cullman, it continues its northeastward orientation. It passes through Arab before turning eastward as it approaches its terminus at Guntersville.