I-57 essentially serves as a shortcut route for travelers headed between the Southern United States (Memphis, New Orleans, etc.)

The Interstate ends at unsigned exit 124 in Walnut Ridge, where US 67 continues north to Pocahontas and US 412 splits off to the east.

To the east of Charleston, the US 60 concurrency ends after about 12 miles (19 km) when I-57 meets US 62/Route 77, with US 60 heading eastward and I-57 Bus.

In Mount Vernon, I-57 has a short concurrency with I-64 while making two diamond interchanges with the city's streets.

The oldest segment of I-57 is a 6.2-mile (10.0 km) strip running east of Bradley to Kankakee labeled on the 1959 Illinois state highway map.

[citation needed] A 21.5-mile (34.6 km) section of I-57 in Jefferson County from Bonnie (using a temporary road that is still partially visible from the northbound lanes) to IL 161 later opened on December 9, 1969.

[7] The portion of I-57 in Chicago (known as the Dan Ryan West Leg Extension) was constructed and opened in segments between 1963 and 1970.

[14] I-57 is slated to eventually be extended west along US 60 to Poplar Bluff, Missouri, and then south along the US 67 corridor to North Little Rock, Arkansas, ending at I-40.

[16] In April 2016, a provision designating US 67 from North Little Rock to Walnut Ridge, Arkansas, as "Future I-57" was added into the federal fiscal year 2017 Transportation, Housing and Urban Development funding bill and officially became law in 2017.

[17] On November 7, 2024, the section of US 67 between North Little Rock and Walnut Ridge, Arkansas, was officially designated as I-57 by ArDOT.

[18] Missouri has already converted 62 miles (100 km) of the US 60/US 67 corridor between Sikeston and US 160/Route 158 near Harviell to a mixture of freeway and expressway segments.

[19] This leaves about twelve miles (19 km) of new freeway between US 160/Route 158 to the Arkansas state line to be constructed.

[21] The Arkansas Department of Transportation (ArDOT) announced in September 2023 that work to extend Future I-57 in Clay County would begin in late 2024 or early 2025 depending on when contracts are let along with completion of the final design process.

From this diamond interchange, it runs north concurrently with Route 105 along South Main Street into the city center.