| Interstate 55 (I-55) – Runs north-south through Mississippi, connecting Louisiana to Tennessee, passing through key cities such as Jackson and McComb. |
| Interstate 20 (I-20) – Traverses east-west across central Mississippi, linking Vicksburg, Jackson, and Meridian, facilitating travel between Louisiana and Alabama. |
| Interstate 10 (I-10) – Crosses the southern part of the state, connecting Gulfport and Biloxi, and serving as a major east-west corridor along the Gulf Coast. |
| Interstate 22 (I-22) – Extends from the northwest corner of Mississippi near Byhalia to Birmingham, Alabama, passing through Tupelo, providing a vital link between the two states. |
| Interstate 22 (I-22) – Extends from the northwest corner of Mississippi near Byhalia to Birmingham, Alabama, passing through Tupelo, providing a vital link between the two states. |
| U.S. Route 61 (US 61) – Known as the "Blues Highway," it runs along the western edge of Mississippi, connecting cities such as Vicksburg and Clarksdale, and continuing into Louisiana and Tennessee. |
| U.S. Route 82 (US 82) – An east-west highway crossing northern Mississippi, connecting Greenville, Greenwood, and Columbus, and extending into Alabama and Arkansas. |
| U.S. Route 84 (US 84) – Traverses east-west across southern Mississippi, linking Natchez, Brookhaven, and Laurel, and continuing into Alabama. |
| U.S. Route 90 (US 90) – Parallels I-10 along the Gulf Coast, connecting Bay St. Louis, Gulfport, and Biloxi, serving as an important route for coastal communities. |
