Interstate 22 (abbreviated I-22), when completed, will follow the U.S. Highway 78 corridor along a 213-mile (343-km) route from Memphis, Tennessee, to Birmingham, Alabama.[2] Future I-22 will connect Interstate 55 and Interstate 40 in the northwest to Interstate 65 and Interstate 20 in the southeast, passing through or close to the towns of Holly Springs, Mississippi; New Albany, Mississippi; Tupelo, Mississippi; Hamilton, Alabama; Winfield, Alabama; and Jasper, Alabama.

The part of I-22 east of Fulton, Mississippi, was approved in 1978 as Corridor X, part of the Appalachian Development Highway System. Parts of the highway have been under construction ever since. Two stretches of the interstate remain to be completed. One stretch is in Alabama and totals approximately 6 miles in length from Cherry Avenue in Forestdale to U.S. Highway 31 in Birmingham. This section includes the interchange with Interstate 65. The other stretch is from the Mississippi/Tennessee state line to its terminus in Memphis. The exact location of the western terminus has not been decided as of yet, but Interstate 269 (when completed) and Interstate 240 have been discussed as possible termini. Funding for the remaining sections has been a priority for U.S. Sen. Richard C. Shelby (R-Ala.), who served as Chairman of Senate Transportation Subcommittee. In 2004 Corridor X was designated as Future Interstate 22 by Public Law No: 108-199, and the designation was made official on April 18, 2005. In Alabama, blue signs reading "FUTURE/I-22/CORRIDOR" at left and an I-22 shield with "FUTURE" instead of "INTERSTATE" at right were unveiled April 18, 2005.

Approximately 91 miles of Interstate 22 is open to traffic in Alabama. The section of the route between the Mississippi state line and Jasper was completed in 2005. A 13-mile section of I-22 between Dora and Forestdale was opened to local traffic only (no thru trucks) in June 2007. Another 12-mile segment between Jasper and Dora was opened on November 14, 2007. Interstate 22 now travels the full length between suburban Birmingham and suburban Memphis, stopping short of the proposed major interstate connections: I-240 and I-65. Exits on the Jasper Bypass portion of I-22 were originally numbered using a kilometer-based sequence in anticipation of U.S. metrification, but have since been renumbered to a mileage-based sequence.

Current plans call for Interstate 22 to be completed to I-65 in 2010, with the 14-bridge stack interchange in Birmingham being completed in 2010. Construction is well underway for the segment between Cherry Avenue in Forestdale to a spot about .5 mile shy of I-65 near Fultondale. This segment includes an interchange with Coalburg Road. A project to widen I-65 to four lanes in either direction has begun from just south of the upcoming I-22/I-65 interchange southward to the 16th Street interchange. Under the present design, I-22 will terminate at I-65, but the mainline highway will continue east beyond I-65 as a long pair of ramps to US-31. After I-22 signs do go up on the US-78 freeway, the US-78 designation will revert back to its original pre-interstate alignment.

At the western end of the route, the connection between Interstate 22 and the other interstates in the vicinity of Memphis is most likely to make use of the Interstate 269 Outer Memphis Beltway, which is currently in various stages of planning and construction. One possible routing takes I-22 westward along I-269 to the existing I-55/I-69 interchange near Hernando, Mississippi.

Corridor X was also designated as High Priority Corridor 10 in the National Highway System Designation Act of 1995 and High Priority Corridor 45 in subsequent legislation.

I-22 map