U.S. Highway 20 (US 20) in Iowa is a major east–west artery which runs across the state, separating the northern third of Iowa from the southern two-thirds. It enters Iowa from Nebraska, concurrent with Interstate 129 (I-129) and US 75, crossing the Missouri River at Sioux City. US 20 runs in a more-or-less straight line across Iowa, paralleling 42° 27' N. It leaves Iowa in Dubuque by crossing the Mississippi River into Illinois. Since October 2018, US 20 is a four-lane divided highway for its entire length in Iowa.

In the US state of Iowa, Interstate 29 (I-29) is a north–south Interstate Highway which closely parallels the Missouri River. I-29 enters Iowa from Missouri near Hamburg and heads to the north-northwest through the Omaha–Council Bluffs and the Sioux City areas. It exits the state by crossing the Big Sioux River into South Dakota. For its entire distance through the state, it runs on the flat land between the Missouri River and the Loess Hills.