It begins at the Missouri state line southwest of Northboro and travels north in a zigzag pattern through Shenandoah, Avoca, Denison, and Cherokee.

It heads north for about ten miles (16 km) when it eases to the east and aligns with the Fremont–Page county line.

Prior to 2003, Iowa 83 continued west to Minden, but that roadway is now known as County Road G18 (CR G18).

After curving around Defiance, the road enters Crawford County and then meets Iowa 141 from the east.

Just beyond the city limits of Denison, Iowa 141 splits off to the west as US 59 remains on a northwestern vector.

[2][3] South of Schleswig, the highway straightens out to the north and stays in that direction until it reaches Iowa 175 east of Ida Grove.

As the highways enter Ida Grove, there is an 8-acre (3.2 ha) manmade lake featuring a half-scale replica of HMS Bounty.

Godbersen also built a few buildings and structures in a castle motif in order to stoke pride in the community.

Just after crossing the Little Sioux River in downtown Cherokee, US 59 meets Main Street.

After a brief overlap of US 18, US 59 heads due north on a straight line for all but the last mile of its time in the state.

[3] US 59 enters Minnesota about 2 miles (3.2 km) east of where Iowa 60 crosses the state line.

[5] In 1919, the Iowa General Assembly passed a bill that created a fund for improving and hard-surfacing nearly 6,300 miles (10,100 km) of primary roads in the state.

Route numbers were painted onto telegraph and telephone poles in order to guide travelers without the need for maps.

4, which originally extended from the Missouri state line to Minnesota, had its northern end truncated at US 20 between Schaller and Early upon creation of the U.S. Highway System in 1926.

[14] An extension of US 73 was approved, but on the Nebraska side of the Missouri River north to Sioux City.