It parallels US 75 for nearly its entire route, never much more than 100 miles (160 km) away, until it veers southwest in Houston, Texas.

At the Mexican border, it ends at the World Trade International Bridge in Laredo, Texas.

In Laredo, US 59 is co-signed with both I-69W and Loop 20, and has an intersection of I-35 which ends at the Juarez-Lincoln International Bridge.

[5][6] Until 2012, US 59 passed through Ottawa, Kansas, and had to be shut down or detoured every time the Marais Des Cygnes floodwall gates were closed across the highway.

North of the U.S. 40 and 59 Bridges, it splits with US 40 as it joins US 24 briefly and jogs back west before resuming a northerly course.

It continues north to Nortonville, then northeast to Atchison, where it crosses the Missouri River over the Amelia Earhart Bridge.

Except for small stretches of expressway near Avoca, Denison, and Holstein, the entire length of US 59 in Iowa is an undivided two-lane road.

US 59 enters Minnesota south of Worthington, just one mile (1.6 km) east of Bigelow.

[8][9] In 1934, a coalition of government officials from Missouri, Iowa, and Minnesota agreed to sign the current US 59 as Highway 73 in an attempt to extend US 73 north from Atchison, Kansas.

However, the American Association of State Highway Officials (AASHO) approved the route as US 59, instead.

A new highway and border crossing were built north of Lancaster on the present alignment in 1950.

[citation needed] In 1933, much of the present US 59 and the entirety of US 96 in Texas were originally proposed to be part of US 71.

Under this plan, discussed at a meeting of the United States Good Roads Association in Beaumont, US 71 was to be diverted out of Louisiana altogether and instead rerouted from the Texarkana area southward through East Texas.

[10] A large portion of US 59 is proposed to become part of the future extension of I-69, I-69W and I-369 through Texas, allowing the current alignment and right-of-way to be upgraded without the need for government environmental studies or extensive eminent domain proceedings.