Interstate 57 (I-57) is a north–south Interstate Highway in Missouri and Illinois that parallels the old Illinois Central Railroad for much of its route. It runs from Sikeston, Missouri, at I-55 to Chicago, Illinois, at I-94. I-57 essentially serves as a shortcut route for travelers headed between the Southern U.S. and Chicago, bypassing St. Louis, Missouri, and Springfield, Illinois. Between the junction of I-55 and I-57 in Sikeston and the junction of I-55 and I-90/I-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 and the 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, even though I-55 also goes to Chicago. A southward extension of I-57 from its current southern terminus to Little Rock, Arkansas, is currently in various stages of development.

Sikeston is a city located both in southern Scott County and northern New Madrid County, in the state of Missouri, United States. It is situated just north of the "Missouri Bootheel", although many locals consider Sikeston a part of it. By way of Interstate 55, Interstate 57, and U.S. Route 60, Sikeston is close to the halfway point between St. Louis and Memphis, Tennessee and is four hours from Nashville.