After crossing into Linn County, the three routes enter the Cedar Rapids city limits near Eastern Iowa Airport.

As it approaches downtown and the Cedar River, the freeway takes a tight, 90-degree turn to the east, crosses the river and squeezes between a Quaker Oats Company plant and Alliant Energy PowerHouse, before turning back 90 degrees to the north.

Between downtown and the Coldstream–29th Street interchange, I-380 serves as a dividing line between residential areas to the east and industry to the west.

Toward the northern end of Cedar Rapids, industry is replaced with commerce as I-380/Iowa 27 meet Iowa 100, locally known as Collins Road, at a volleyball interchange.

The three routes pass the eastern Waterloo suburbs of Raymond, Evansdale, and Elk Run Heights.

Almost immediately after crossing the Cedar River again, I-380 splits away from US 20 and Iowa 27 and rejoins US 218 at a three-level stack interchange.

[5] I-380 ends at the traffic light at Mitchell Avenue one-half mile (800 m) north of the interchange which serves the Crossroads Center.

[2] The Interstate was originally scheduled to be open by December 25, 1984, but weather delays pushed back the construction timetable.

[11] During the construction process in March 2021, the eastbound ramps from I-80 utilized the new flyover bridges while transit from northbound US 218 to westbound I-80 required a detour via the next interchange at Forevergreen Road.

The Cedar River crested at over 31 feet (9.4 m) on June 13, causing hundreds of millions of dollars in damage.

A new diverging diamond interchange will also be built at Wright Brothers Boulevard near the Eastern Iowa Airport.