Interstate 57 (I-57) is an Interstate Highway in Missouri and Illinois that parallels the old Illinois Central rail line for much of its route. It goes from Sikeston, Missouri, at Interstate 55 to Chicago, Illinois, at Interstate 94. I-57 essentially serves as a shortcut route for travelers headed between the south (Memphis, New Orleans, etc.) and Chicago, bypassing St. Louis, Missouri. Between the junction of I-55 and I-57 in Sikeston, Missouri and the junction of I-55 and I-90/94 in Chicago, I-55 travels for 436 miles (702 km), while the combination of I-57 and I-94 is only 396 miles (637 km) long between the same two points. In fact, both the control cities on the overhead signs, as well as destination mileage signs, reference Memphis along southbound I-57, even as far north as its northern origin at I-94 in Chicago. Likewise, at its southern end, Chicago is the control city listed for I-57 on signs on northbound I-55 south of Sikeston, Missouri, even though I-55 also goes to Chicago.

As of 2010[update], I-57 has no spur routes, nor are any planned in the near future. At a length of just over 386 miles (621 km), it is the longest two-digit interstate highway without an auxiliary route. I-57 has one Business Loop in Charleston.

In the state of Missouri, Interstate 57 runs northbound from Sikeston to the Cairo I-57 Bridge over the Mississippi River south of Cairo, Illinois.

After ending southbound at Interstate 55, the highway continues as U.S. Route 60, which meets U.S. Route 67 at Poplar Bluff, Missouri, and from there U.S. Route 67 goes south to Little Rock, Arkansas. The state of Missouri has proposed extending the I-57 designation down this corridor. However, this plan conflicts with Arkansas' plans to extend the Interstate 30 designation north on U.S. Route 67, a road of which a long section already meets Interstate Highway standards.[citation needed]

From the start of I-57 northbound, the US 60 concurrency goes about 12 miles.

In the state of Illinois, Interstate 57 runs from the bridge over the Mississippi River north to Chicago. I-57 is the longest Interstate Highway in Illinois. Its route follows essentially the earlier route of US 51 in southernmost Illinois (US 51 has been diverted to I-57 where I-57 has always been close to old US 51 between Future City and Dongola) before taking a northeastward diagonal to Illinois 37, which remains intact as a town-to-town through route, past its interchange with Interstate 24 (the northwestern terminus of Interstate 24) near Pulleys Mill and a short duplex with Interstate 64 near Mount Vernon north to Effingham, where it has a short concurrence with Interstate 70. It then follows US 45 bypassing cities of Champaign and Urbana (where it meets Interstates 72 and 74), and heads north to Onarga whereafter it follows the formerly duplex path of US 45 and (now decommissioned in most of Illinois) old US 54 to Kankakee. At Kankakee it heads northward largely parallel to the now decommissioned route of old US 54 (since renumbered largely as Illinois 50) into greater Chicago, meeting Interstate 80 in Chicago suburbs and feeding Interstate 94 on Chicago's South Side.

Although I-57 serves as a long-distance bypass of St. Louis, the section between Mount Vernon and Pulleys Mill contains the most direct Interstate route between St. Louis and cities largely to the southeast of St. Louis (including Nashville and Atlanta). It serves as the northwestern terminus of Interstate 24 that leads southeastward to those cities and as the eastern terminus of Interstate 72 near Champaign.

The route is an easy way to reach Shawnee National Forest in the southern tip of the state. It also serves as a major artery for college students in the state, running near Southern Illinois University in Carbondale, Rend Lake College in Ina, Eastern Illinois University in Charleston, Parkland College in Champaign, University of Illinois at Urbana-Champaign in Urbana-Champaign, Kankakee Community College in Kankakee, Olivet Nazarene University in Bourbonnais, and Governors State University in University Park. Interstate 57 currently does not have an intersection with Interstate 294 (Tri-State Tollway) in northeastern Illinois, though one is planned. It is one of only a few examples where Interstates cross but do not have interchanges with each other. Vehicles are directed to use Interstate 80 to access Interstate 294 instead, though U.S. Route 6 is another option.

I-57 remains the only Chicago expressway that does not have a commonly-used name. Its Chicago-area portion was formerly known as the Dan Ryan Expressway–West Leg.

A 21.5 mile section of I-57 in Jefferson County from Bonnie (using a temporary road that is still partially visible from the northbound lanes) to Illinois Route 161 opened on December 9, 1969. The final section of I-57 in Illinois opened in December 1971 at Paxton, IL.

The portion of Interstate 43 from Milwaukee to Green Bay was originally numbered as Interstate 57. The number was changed due to the existence of I-57 in Illinois.

Interstate 57 may eventually be extended west along the U.S Route 60 corridor and then turn south along the future U.S Route 67 freeway corridor and head south to Little Rock, Arkansas. However, it conflicts with Arkansas's plans to extend Interstate 30 along that alignment.

Illinois Department of Transportation has proposed widening a section of I-57 to six lanes of traffic from I-24 to I-64. This section of interstate has some of the highest AADT on I-57 outside of the Chicago metropolitan area, with truck traffic amounting up to 30% of all traffic in spots. This section of I-57 has been the site of several interstate closing accidents in the past 10 years, including an incident involving a train derailment over the interstate near Benton in July 2004 and several fatal accidents in various construction zones. The section in Mt. Vernon is due to be widened by 2013 with construction having begun in late 2011.

The IDOT and the Illinois Toll Highway Authority have announced plans to build an interchange at the junction of Interstate 57 with Interstate 294, one of only two locations where interstate highways cross without an interchange.

The Champaign, Illinois, band Braid recorded a song titled "Interstate 57" on its debut album, Frankie Welfare Boy Age Five.