Within the southwestern suburbs and the South Side, US 20 runs concurrently with US 12 and US 45 (later US 41), ultimately leaving Illinois on Indianapolis Boulevard.

As the highway enters Illinois across the Julien Dubuque Bridge, it continues southeasterly for a while, paralleling the Upper Mississippi River before turning east into the rugged country of the Driftless Area in Jo Daviess County, then turning flat and straight west of Stockton and entering Stephenson County.

The Ulysses S. Grant Home, a national landmark, fronts near the highway at the eastern edge of Galena.

Between Freeport and Rockford, the route is a four-lane divided highway with two traffic light-controlled intersections, at Pecatonica Road and at Winnebago Road/Elida Street.

East of Rockford, the routing of US 20 runs parallel with I-90; US 20 serves minor cities that are not accessible from the Jane Addams Memorial Tollway.

It is a four-lane divided highway from I-39 to just east of Belvidere; for the rest of this segment, it is a winding, rural two-lane road.

US 20 travels through the downtowns of the small towns and unincorporated areas of Garden Prairie, Harmony and Starks, as well as the city of Marengo.

This combination later joins with US 41, where the three routes follow Ewing Avenue and Indianapolis Boulevard, which are the last portions of US 20 prior to its crossing the state line into Indiana.

In 1935, concerned about increasing numbers of traffic, residents of Elgin laid plans to build a bypass.

[5] The segment of the Elgin Bypass between McLean Boulevard and Grace Street (IL 25), including the Fox River bridge, was opened first.

[8][9] In 2019, the interchange between the Elgin Bypass and Randall Road received a $9-million (equivalent to $10.6 million in 2023[7]) upgrade so that northbound Randall Road traffic can enter the eastbound Elgin Bypass without making a left turn at a traffic light.

[11] Long range plans call for US 20 to be upgraded to a four lane highway from Rockford to East Dubuque.

The project dates back to the 1970s, when a major supplemental freeway system was proposed in Illinois.

The remaining gap between Freeport and Galena is planned to be filled, but efforts have stalled in recent years, mainly due to funding issues.