Interstate 380 (I-380) is a 73-mile (117 km) auxiliary Interstate Highway in eastern Iowa. The route extends from I-80 near Coralville to Waterloo. I-380 connects the cities of Cedar Rapids and Waterloo, the state's second- and sixth-largest cities, respectively, to the Interstate Highway System. Except for its last 1.5 miles (2.4 km) north of U.S. Highway 20 (US 20), I-380 runs concurrently with Iowa Highway 27 (Iowa 27), which represents Iowa's portion of the 560-mile (900 km) Avenue of the Saints highway connecting Saint Louis, Missouri, with Saint Paul, Minnesota.

Interstate 80 (I-80) is a transcontinental Interstate Highway in the United States, stretching from San Francisco, California, to Teaneck, New Jersey. In Iowa, the highway travels west to east through the center of the state. It enters the state at the Missouri River in Council Bluffs and heads east through the southern Iowa drift plain. In the Des Moines metropolitan area, I-80 meets up with I-35 and the two routes bypass Des Moines together. On the northern side of Des Moines, the Interstates split and I-80 continues east. In eastern Iowa, it provides access to the University of Iowa in Iowa City. Northwest of the Quad Cities in Walcott is Iowa 80, the world's largest truck stop. I-80 passes along the northern edge of Davenport and Bettendorf and leaves Iowa via the Fred Schwengel Memorial Bridge over the Mississippi River into Illinois.