Texas

I-20 begins in Scroggins Draw at a fork with I-10. From there, the highway travels east-northeastward through Odessa, Midland, and Abilene before turning eastward toward the Dallas–Fort Worth metroplex. The La Entrada al Pacífico corridor runs along I-20 between US Route 385 (US 385) and Farm to Market Road 1788 (FM 1788). Between Monahans and I-10, I-20 has an 80-mile-per-hour (130 km/h) speed limit.

From the highway's opening in the 1960s through 1977, I-20 originally went through the heart of the metroplex via the Dallas–Fort Worth Turnpike. This old route is now signed I-30 (Dallas–Fort Worth Turnpike and from US 80/I-30 intersection at Mesquite to Downtown Dallas), US 80 (former stretch between I-635 and Terrell), and Spur 557 (bypass around Terrell). In 1977, I-20 was rerouted to go through the southern sections of Fort Worth, Arlington, Grand Prairie, Dallas, and Mesquite. It split off from the old route initially at I-820 in west Fort Worth the later on at its current junction near Aledo in Parker County. It rejoins the old route near Terrell. Part of I-20 in Dallas used to be signed as I-635 and shares the Lyndon B. Johnson Freeway name with the remainder of I-635. Parts on the south side of Fort Worth were originally signed as I-820.^[3]

I-20 continues eastward from Terrell, bypassing Tyler, Longview, and Marshall before crossing the Louisiana border near Waskom.

Louisiana

In Louisiana, I-20 roughly parallels US 80 through the northern part of the state.

Entering the state from near Waskom, Texas, the highway immediately enters the Shreveport–Bossier City metropolitan area, intersecting I-49 near downtown Shreveport and passing close to Barksdale Air Force Base in Bossier City.

I-20 traverses mainly rural, hilly terrain, bypassing Minden, Grambling, and Ruston before reaching Monroe.

From Monroe, I-20 enters flatter terrain as it approaches the Mississippi River. Before crossing the Mississippi, the highway passes Tallulah. At the Mississippi River, I-20 leaves Louisiana and enters Vicksburg.

Mississippi

Upon entering Mississippi by crossing the Mississippi River, I-20 immediately enters Vicksburg. Between Edwards and Clinton, the highway mostly follows the original two-lane routing of US 80. In Jackson, I-20 sees a short concurrency with both I-55 and US 49. Also in Jackson is an unusually expansive stack interchange, at the junction of I-20, I-55 north, and US 49 south. The interchange replaces a former directional interchange at I-55 north and a cloverleaf interchange at US 49. From the stack, I-20 continues eastward to Meridian, where it begins the nearly 160-mile (260 km) overlap with I-59.

The route of the Mississippi section of I-20 is defined in Mississippi Code § 65-3-3.

Alabama

I-20 (along with I-59) crosses the Alabama state line near York, and it stays conjoined as it passes through western Alabama and Tuscaloosa. At Birmingham, the two highways pass through downtown together before splitting at exit 130 just east of Birmingham–Shuttlesworth International Airport. I-20 continues eastward through Oxford–Anniston and the Talladega National Forest, passing by Talladega Superspeedway in the process, which is visible from the highway.

Also in Birmingham, the intersection of I-20/I-59 and I-65 was known as a Malfunction Junction because of the interchange's somewhat-confusing design, and the number of traffic accidents that occurred there. This section of the Interstate and its interchanges have since been reconfigured.^[4][5]

Georgia

I-20 enters Georgia near Tallapoosa and after passing through western Georgia, it enters the Atlanta metropolitan area. On clear days, eastbound motorists get their first view of Downtown Atlanta as they come over the top of Six Flags Hill. The Six Flags Over Georgia amusement park is easily visible off exit 46 eastbound. The highway then passes through the center of Atlanta, meeting with I-75 and I-85, which share a common expressway (the Downtown Connector). It continues through the Atlanta metropolitan area eastward and through the eastern half of Georgia until it exits the state, crossing the Savannah River at Augusta.

Throughout the state, I-20 is conjoined with unsigned State Route 402 (SR 402). Also, I-20 from the Alabama state line to I-285 in Atlanta is named the "Tom Murphy Freeway", but it is called the "Ralph David Abernathy Freeway" within I-285. The Interstate Highway is also named the Purple Heart Highway from I-285 in DeKalb County to US 129/US 441/SR 24 in Madison, Georgia, and it is called the Carl Sanders Highway from US 129/US 441/SR 24 to the South Carolina state line.

South Carolina

Upon leaving Augusta, I-20 crosses the Savannah River and enters the Palmetto State and heads northeastward, bypassing Aiken and Lexington before reaching the state capital of Columbia, which can be reached most directly by taking I-26 east at exit 64 ("Malfunction Junction"), then, almost immediately, I-126/US 76.

At Columbia, I-20 bypasses the city to the north and again turns northeastward, bypassing Fort Jackson and Camden. After crossing the Wateree River, it turns due east and passes by tiny Bishopville, before reaching the Florence area. It is near Florence where I-20 sees its eastern terminus at I-95. However, for about two miles (3.2 km), the highway continues into Florence as I-20 Bus.

I-20 in the Palmetto State is known as either the J. Strom Thurmond Freeway or John C. West Freeway. The first section to be completed was the bridge over the Savannah River in 1965; the last, the section between US 401 and I-95 (including the business spur), opened in August 1975.