The major cities that I-20 connects to include Dallas-Fort Worth, Texas; Shreveport, Louisiana; Jackson, Mississippi; Birmingham, Alabama; Atlanta, Georgia; and Columbia, South Carolina.

I-20 runs from Texas to South Carolina serving major southern economic hubs such as Dallas–Fort Worth and Atlanta.

The La Entrada al Pacífico corridor runs along I-20 between US Route 385 (US 385) and Farm to Market Road 1788 (FM 1788).

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.

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

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.

On clear days, eastbound motorists get their first view of Downtown Atlanta as they come over the top of Six Flags Hill.

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.

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.

After crossing the Wateree River, it turns due east and passes by tiny Bishopville, before reaching the Florence area.

I-20 was built in 1957 connecting Texas to the east coast running through Shreveport, Ruston, and Monroe making it their first Interstate.

Due to anti-freeway sentiments, this I-420 was never completed, and the already-built portion has been signed as State Route 154 (SR 154)/SR 166, named the Langford Parkway (formerly the Lakewood Freeway).