Interstate 65 (I-65) meanders across 366 miles (589 km) of the Alabama countryside linking six of the state's 10 largest cities. The highway links together many important roadways that make commerce inside and outside of the state's boundaries possible. It starts at I-10 near Mobile. The route passes through the major cities of Montgomery, Birmingham, Decatur, Huntsville, and Athens before entering Tennessee in the north near the town of Ardmore, Alabama.

Interstate 10 (I-10) is a part of the Interstate Highway System that runs from Santa Monica, California, to Jacksonville, Florida. In Alabama, the Interstate Highway runs 66.269 miles (106.650 km) from the Mississippi state line near Grand Bay east to the Florida state line at the Perdido River. I-10 is the primary east–west highway of the Gulf Coast region of Alabama. The highway connects Mobile, the largest city in South Alabama, with Pascagoula, Mississippi, to the west and Pensacola, Florida, to the east. Within the state, the highway connects Mobile and Mobile County with the Baldwin County communities of Daphne and Fairhope. I-10 connects Mobile and Baldwin County by crossing the northern end of Mobile Bay and the southern end of the Mobile-Tensaw River Delta via the George Wallace Tunnel in Mobile and the Jubilee Parkway viaduct system between Mobile and Daphne.