Interstate 22 (I-22) is an Interstate highway that, upon completion, will follow the U.S. Route 78 (US 78) corridor on a 213-mile-long (343 km) route from Memphis, Tennessee, to Birmingham, Alabama. I-22 will connect I-240, I-40, I-55, and I-69 (indirectly) in the northwest with I-65 and (indirectly) I-20/I-59 in the southeast. Hence, I-22 will help form a freeway to connect downtown Atlanta with Birmingham, Memphis, Little Rock, Fort Smith, and Oklahoma City.

Along its way through the two states, I-22 will also serve the towns of Jasper, Winfield, and Hamilton, Alabama and Fulton, Tupelo, New Albany, and Holly Springs, Mississippi. Major portions of this highway have either been built new or converted to Interstate Highway standards as of early 2011. According to the American Association of State Highway and Transportation Officials (AASHTO), a connection to another Interstate highway must be completed before this highway is officially designated as part of the Interstate Highway System. As of 2013 an interchange with I-65 near Birmingham is under construction. An interchange to be constructed near Byhalia designated as I-269 would be the western terminus of I-22. The portion of I-269 just north of this area was completed by early 2013.