And now we enter Iowa, continuing our tour through the Midwest and the breadbasket of America. The name derives from the Ioway people, itself a Sioux term and not their endonym, who inhabited the region in antiquity and subsequent to their forced relocation today exist as two descendent tribes in Oklahoma and collectively Kansas and Nebraska. The entirety of Iowa's US 6 routing is the continuation of former US 32 from Omaha (Part 21) along the 1920 Detroit-Lincoln-Denver Highway (Part 20) until US 6's expansion in 1934. It, in turn, was incorporated out of the 1910 River-To-River Road (a/k/a the River-To-River Highway), Iowa's oldest auto trail extending from the Missouri River and the Nebraska state line which we just crossed to the Mississippi River and the Illinois state line (Part 25), and the more obscure Great White Way/White Pole Road established the same year from Council Bluffs to Des Moines; the R-to-R ran somewhat more northerly than the White Pole, and much of what we will travel in western Iowa corresponds more to the latter than the former. The River-To-River shield at right dates from approximately 1912. Although some portion of the original alignments are bypassed and we will not travel them all, many remain US 6 or otherwise state or local highways, and the entire overall routing remains as important to the modern motorist as it did in 1910. Some of these alignments were late relinquishments to the local jurisdiction by the 2002 Road Tax Use Fund Commission and subsequent legislation, which transferred 712 miles of state highway to cities and counties.

In 1920 Iowa started adding primary numbers to its routes, selecting the same number if the route crossed a state line. As US 6's ancestor in those pre-US highway days was NE 6, the alignment entering the state here was thus signed IA 6. A minor renumbering occurred in 1926 to avoid collisions with the new US highways as then-IA 6 became US 32 (a second, larger Great Renumbering occurred in 1969). The Iowa highway marker, then as now, was a simple circle with the route number and for some number of years the state name. Like in eastern Nebraska much of US 6 has been superseded by Interstate 80, largely built along the older highway's routing between 1958 and 1972 when the final leg across the Missouri into Omaha was constructed; US 6 today is co-signed with several of its alignments and a I-80 spur. For that matter I-80 also completely superseded the planned Iowa Turnpike toll road, rendered obsolete by the passage of the Federal Aid Highway Act of 1956 and never built. Historically undermaintained, I-80 suffered under substandard conditions for many years until a massive refurbishment with federal dollars in 1985.