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.

U.S. Highway 75 (US 75) is a United States Highway in northwestern Iowa. It begins at the Missouri River on a bridge with Interstate 129 (I-129) and US 20. Immediately upon landing in Iowa from Nebraska, I-129 ends at an interchange with I-29. US 20 and US 75 continue around Sioux City on a four-lane expressway until US 20 exits to the east. US 75 heads to the north-northeast, parallel to the Floyd River, until Le Mars. There, Iowa Highway 60 (Iowa 60) continues northeastward on the expressway while US 75 heads due north. Near Hull, it is briefly overlapped by US 18. It leaves the state and enters Minnesota north of Rock Rapids.