U.S. Route 6 (US 6) is an east–west U.S. highway which runs 317 miles (510 km) across the U.S. state of Iowa. It is signed in places as the Grand Army of the Republic Highway. Like all state highways in Iowa, it is maintained by the Iowa Department of Transportation. The route begins at the Missouri River crossing at Council Bluffs. From there, it travels east through Oakland and Atlantic, Iowa. North of Atlantic, US 6 overlaps Interstate 80 (I-80) until De Soto. Between De Soto and Adel, it overlaps U.S. Route 169 (US 169) before splitting off to the east towards Des Moines. Through Des Moines, it runs about one mile (1.6 km) south of the Interstate 35 / Interstate 80 corridor.

At Altoona, it again overlaps I-80 until Newton. At Newton, it splits away from I-80 and passes near of through the cities of Kellogg, Grinnell, Victor, Marengo, the Amana Colonies, and Tiffin before entering the Coralville / Iowa City area. Through Coralville and Iowa City, US 6 has no direct access to I-80, I-380, or US 218; it relies on other routes like Iowa Highway 1 (Iowa 1) and Iowa 965 to provide access. From Iowa City, it heads to the east-southeast through West Liberty and Atalissa. Near Wilton, it heads north to I-80 where it again overlaps to Davenport. At Davenport, it briefly overlaps Interstate 280 and U.S. Route 61 before entering the city. It intersects Interstate 74 on the eastern side of Davenport and enters Bettendorf before leaving Iowa for Illinois.

Dating back to 1910, the route US 6 follows was originally the Great White Way and River-to-River Road, both were historic auto trails which connected Council Bluffs and Davenport. When the U.S. Highway System was created in 1926, it was designated U.S. Route 32. US 32 was renumbered in 1931 as US 6 was extended to the west coast. As the Interstate Highway System was expanding in the 1950-1970s, US 6's importance as a cross-state route was diminished by Interstate 80. As a result, the least-traveled sections of the route were moved onto I-80.

U.S. Route 6 crosses the Missouri River via the Grenville Dodge Memorial Bridge into Council Bluffs, Iowa with Interstate 480 (I-480). Just 3⁄4 miles (1.2 km) into the state, I-480 ends at an interchange with Interstate 29. US 6 heads east along Broadway, where it is overlapped by Iowa Highway 192 (Iowa 192) for just over 1 + 1⁄2 miles (2.4 km). On the eastern side of Council Bluffs, it intersects Interstate 80 and continues due east. Near Oakland, it overlaps the north–south U.S. Route 59 for 2 miles (3.2 km). Near Lewis, it turns to the north-northeast until it reaches Atlantic. In Atlantic, it turns back to the east and heads towards downtown where it meets Iowa Highway 83. US 6 / Iowa 83 travel together to the eastern side of Atlantic where they meet U.S. Route 71. The three routes run together for 4 miles (6.4 km), when US 6 / US 71 split away from Iowa 83 and continue north to I-80. At I-80, US 6 splits away from US 71 and joins I-80. US 6 overlaps I-80 until De Soto, approximately 50 miles (80 km).

At De Soto, US 6 turns to the north, overlapping U.S. Route 169 for 5 miles (8.0 km) to Adel. East of Adel, US 6 is a four-lane divided highway for 14 miles (23 km), during which, it passes through Waukee, Clive, and Urbandale along Hickman Road, and intersects Interstate 35 / Interstate 80. Over the next 2 miles (3.2 km), it serves as the border between Urbandale and Windsor Heights. At 63rd Street in Des Moines, US 6 intersects Iowa Highway 28. For 1⁄2 miles (0.80 km), US 6 / Iowa 28 run together on Hickman Road. Turning north, they run together for another mile (1.6 km) along Merle Hay Road. At Douglas Avenue, US 6 splits away from Iowa 28 and continues east, becoming Euclid Avenue just west of the Des Moines River. In north-central Des Moines, it intersects U.S. Route 69 and Interstate 235. In northeast Des Moines, it turns to the northeast along Hubbell Avenue, which takes US 6 to Altoona. West of Altoona, it intersects U.S. Route 65 and continues northeast passing Adventureland theme park and Prairie Meadows casino. In northwest Altoona, US 6 intersects I-80 and US 65. US 6 overlaps I-80 for a second time for approximately 25 miles (40 km).

At Newton, US 6 splits away from I-80 at the Iowa Highway 14 interchange. US 6 overlaps Iowa 14 for 1⁄3 miles (0.54 km). It turns off of Iowa 14 and enters the western side of Newton, passing through its downtown area and the Jasper County courthouse. Between Newton and Grinnell, the route becomes hillier and curvier, crossing the North Skunk River near Kellogg. At Grinnell, it intersects Iowa Highway 146 southwest of the Grinnell College campus. East of Grinnell, the route straightens out and it is overlapped by U.S. Route 63 for 2 miles (3.2 km) and by Iowa Highway 21 for 4 miles (6.4 km). Near Victor, US 6 take a northeasterly course through Ladora towards Marengo. At Marengo, it intersects the eastern end of Iowa Highway 212. Five miles (8.0 km) east of Marengo is the western end of Iowa Highway 220. Here, US 6 forms the southern leg of the Amana Colonies Trail. Three miles (4.8 km) later, it's joined by U.S. Route 151 for 2 miles (3.2 km). It heads to the southeast towards Tiffin and passes underneath Interstate 380, but does not have direct access.

At Coralville, US 6 passes underneath Interstate 80, but 1⁄2 miles (0.80 km) to the east, Coral Ridge Avenue provides direct access to I-80. Entering Iowa City, it passes the campus of the University of Iowa, its main hospital, and VA Hospital. US 6 curves to the south to be adjacent to the Iowa River, where it meets and overlaps Iowa Highway 1 for 1⁄2 miles (0.80 km). US 6 and Iowa 1 go in separate directions at a signal controlled intersection, where, less than 1⁄4 miles (0.40 km) away, US 6 crosses the Iowa River. From Iowa City, it heads in an east-southeast direction towards West Liberty. The highway enters West Liberty from the northwest corner and curves southward. At the northern end of Iowa Highway 70, it turns to the east again towards Atalissa and Wilton. Ten miles (16 km) southwest of Wilton, it crosses the Cedar River. Three miles (4.8 km) south of Wilton, the highway overlaps Iowa Highway 38 and the two routes head towards I-80. At I-80, the two routes head in opposite directions on the interstate; US 6 overlaps I-80 for 35 miles (56 km).

On the outskirts of Davenport, US 6 splits away from Interstate 80 and joins Interstate 280 at its western end. U.S. Route 61 also joins I-280 at this interchange, but from the opposite direction. US 6 only overlaps I-280 / US 61 for 4⁄5 miles (1.3 km) before exiting onto Kimberly Road. Heading southeast into Davenport, it is a two-lane highway for 3 miles (4.8 km). At Fairmount Street, it becomes a four-lane divided highway and straightens out to head due east. Near Northpark Mall, it intersects Northwest Boulevard, which becomes Iowa Highway 130 at I-80, and both one-way legs, Welcome Way southbound and Brady Street northbound, of U.S. Route 61 Business, which prior to 2010 was U.S. Route 61. US 6 briefly dips to the southeast and straightens out again towards Interstate 74. It joins I-74 and heads to the south towards Moline, Illinois. For about one mile (1.6 km), I-74 / US 6 forms the boundary of Davenport and Bettendorf. The two routes completely enter Bettendorf and descend into the Mississippi River valley, where they meet U.S. Route 67 at a complex series of exit and entrance ramps. They then ascend the Iowa-Illinois Memorial Bridge, known locally as the I-74 Bridge, and cross the Mississippi River into Illinois.

Before the U.S. Highway System came into being in 1926, roads in Iowa were maintained and promoted by local organizations which sought to drive traffic into their communities. Two such organizations created virtually parallel routes connecting Council Bluffs and Davenport via Des Moines. The routes, the southern Great White Way and northern River-to-River Road, eventually merged into the Whiteway-7-Highway. The new route followed the Great White way from Council Bluffs to Des Moines and the River-to-River Road from Des Moines to Davenport. In 1926, the Whiteway-7-Highway became U.S. Route 32, which itself became U.S. Route 6 in 1931.

The Great White Way was formed in 1910 by the White Pole Auto Club. The route was built along the Chicago, Rock Island & Pacific Railroad between Council Bluffs and Des Moines. Members of the auto club painted poles along the route white, which lead the route to be known as the White Pole Road. The Great White Way passed through Oakland, Atlantic, Adair, and De Soto. In late 1912, the Great White Way was extended east to Davenport, passing through Pella, Oskaloosa, Washington, and Muscatine. In 1913, when the Iowa State Highway Commission began registering named trails longer than 25 miles (40 km), the Great White Way Association paid the $5.00 fee ($118.00 in 2013 dollars) to become the first official registered highway route on July 30, 1914. When the primary highway system was created, the Great White Way was assigned Primary Road No. 2.

The River-to-River Road (RRR) was also created in 1910 and also connected Council Bluffs and Davenport via Des Moines. This route, however, traveled a more northern route than the Great White Way. The route passed through Neola, Elk Horn, Guthrie Center, Adel, Des Moines, Newton, Marengo, Iowa City, and Wilton. When the highway commission started accepting registered routes, the RRR association planned to register their route as soon as possible. But miscommunication between association members and with the highway commission delayed the actual registration for years. The route became official on April 16, 1918. When the primary highway system was created, the River-to-River Road was assigned Primary Road No. 7.

In 1922, the Whiteway-7-Highway Association filed an application to register the Whiteway-7-Highway with the Iowa State Highway Commission. The commission was concerned with the Whiteway-7's similarity to the Great White Way's name and route markings. The Great White Way was marked with a 6-foot (1.8 m) wide stripe, while the Whiteway-7 would be marked with a 4-foot (1.2 m) stripe with a black circle containing a white seven. Another concern with the new route was since its name contained the number seven, the route would be assigned along Primary Road Nos. 2 and 7. On September 25, 1922, the highway commission swapped the designations of the part of the Great White Way which would become part of the Whiteway-7-Highway with the part of the River-to-River Road which would not become a part. Eight months later, the Iowa State Highway Commission reversed course and restored Primary Road Nos. 2 and 7 to their original alignments. Although disappointed, the Whiteway-7-Highway Association responded by removing the number from their name. On November 27, 1925, the route officially became the Whiteway Highway.

On November 11, 1926, members of the American Association of State Highway Officials approved the plan to create a system of interstate highways across the country. Iowa's Whiteway Highway would take on the designation of U.S. Route 32. For four-and-a-half years, US 32 spanned from Chicago to Council Bluffs. On June 8, 1931, All of the Iowa portion of US 32 was absorbed into a newly-extended U.S. Route 6. The new US 6 also replaced U.S. Route 38 in Nebraska and Colorado. By the end of 1937, US 6 extended from coast to coast. On April 29, 1947, the Iowa General Assembly approved an act designating US 6 as the Grand Army of the Republic Highway, a distinction the route shares in other states.

In the 1950s, the Iowa State Highway Commission began to straighten the route. A section of the highway between Grinnell and Ladora was straightened, which resulted in Brooklyn and Victor being bypassed. Between Dexter and West Des Moines, US 6 swapped alignments with Iowa Highway 90 in 1958. In 1961, US 6 was routed onto the new Interstate 80 from the Iowa 90 interchange to the Baxter exit, currently exit 159. Iowa 90 was extended onto the old US 6 alignment. However, in 1967, those changes were reversed and US 6 was taken off I-80 and put back on the road which had been Iowa 90. Iowa 90 was assigned the section of US 6 between what's now exit 106 along I-80 and exit 69 along I-35.

Since the 1970s, portions of US 6 have been moved permanently onto I-80. The first section, between U.S. Route 71 and Adair, was rerouted in 1972. The abandoned section became an extended Iowa Highway 83 and an Adair County road. In 1980, three lengthy sections were moved onto the interstate: 26 miles (42 km) in western Iowa between Adair and Dexter, 25 miles (40 km) in central Iowa between Altoona and Newton, and 20 miles (32 km) in eastern Iowa between Wilton and Davenport. All three sections were originally kept as state highways, but in 1989, when the Iowa Department of Transportation first showed the new state highways' designations, the central section had been turned over to Polk and Jasper Counties. The western segment was numbered Iowa 925 and the eastern segment Iowa 927.

On July 1, 2003, 15 miles (24 km) between Dexter and Adel were turned over to Dallas County. US 6 was continued along I-80 to the U.S. Route 169 interchange at De Soto, and then along US 169 to Adel. The former segments, Iowa 925 and Iowa 927, were turned over to their respective counties as well.