I-90 traverses 124 miles (200 km) through a variety of settings, from farmland west of the Fox River Valley through the medium-density suburbs west of O'Hare International Airport, through Downtown Chicago, and through the heart of the industrial southeast side of Chicago before entering Indiana.

The Interstate runs along the Jane Addams Memorial Tollway (previously called the Northwest Tollway) from South Beloit to O'Hare Airport, the Kennedy Expressway from O'Hare to the Chicago Loop, the Dan Ryan Expressway from the Loop to the Chicago Skyway, and the Skyway to the Indiana state line.

From this point to the eastern terminus of both highways in Massachusetts, I-90 and US 20 run a roughly parallel routing (though with no concurrency).

As it passes its Randall Road exit, I-90 transitions from the rural farmland seen in Boone and McHenry counties to the western terminus of the Chicago suburbs.

Before meeting I-290, the tollway passes through Hoffman Estates and Schaumburg, routed through a wide variety of surroundings, including housing, retail centers, and forest preserves.

At Elmhurst Road (Illinois 83), the tollway is narrowed to eight lanes, passing north of O'Hare International Airport.

Prior to passing through I-190/I-294 (Tri-State Tollway), Rosemont has a final toll plaza on Devon Avenue (westbound) and River Road (eastbound).

[2] Prior to the opening, the first vehicle to officially travel the new roadway was a covered wagon navigated by local resident John Madsen who took five days to make the journey.

[3] On September 7, 2007, highway officials responding to an effort by state lawmakers renamed the Northwest Tollway to Jane Addams Memorial Tollway, after Jane Addams, the Nobel Peace Prize winner and founder of the Settlement House movement in the US.

The inside shoulders were widened for future transit opportunities, and active traffic management was incorporated into the corridor from IL 59 to the eastern end.

Nearly eight miles (13 km) of elevated roadway, the Chicago Skyway was originally built as a shortcut for cars from State Street, a major north–south street on Chicago's South Side that serves the Loop, to the steel mills on the Southeast to the Indiana state line where the Indiana Toll Road begins.

[16] Historically, the Chicago Skyway was signed as, and was widely considered to be part of, I-90 from the mid-1960s forward (after I-90 in this area had been swapped with I-94).

However, from around 1999 until 2022, the Chicago Department of Transportation worked under a new assumption that they had never received official approval to designate the Skyway as I-90.

[18] Traffic volumes rebounded from the late 1990s onward, partially because of the construction of casinos in Northwest Indiana, along with reconstruction of the Dan Ryan, Kingery, and Borman expressways.

The agreement between the Skyway Concession Company and the City of Chicago marked the first time an existing toll road was moved from public to private operation in the US.

The franchisee terminated the lease with the SCC shortly before, blaming closure on the declining profits as the restaurant was more popular for its restrooms than the food it offered.

I-290 takes a southeasterly dogleg left route accessing the western suburbs and heading eastward into Downtown Chicago.