The highway enters the state east of Columbus, Mississippi, and bears southeast towards Northport and Tuscaloosa, where it crosses over I-20 and I-59 south of town.

[3] After leaving Tuscaloosa, the route continues southeast, passing through the cities of Brent, Centreville, and Maplesville en route to Prattville, on the northern edge of the Montgomery metropolitan area.

This approximately 92-mile (148 km) drive goes through some of the most rural areas of the state, much of it two lanes with the exception of the section from Tuscaloosa to Centreville.

The route then crosses over the Chattahoochee River into Georgetown, Georgia, over Lake Eufaula.

[citation needed] U.S. Route 82 was first designated within the state of Alabama in June of 1934.