It enters the state by crossing the Big Sioux River between Inwood and Canton, South Dakota.

US 18 begins at the Big Sioux River approximately two miles (3.2 km) east of Canton, South Dakota.

The two routes head east toward a diamond interchange with Iowa 60 on the eastern side of town where the business loop ends.

East of Garner, the route takes a north-northeasterly path as it goes through Ventura and skirts the northern shore of Clear Lake.

The two routes, now on a four-lane, controlled-access highway, follow a path which passes to the south of Mason City.

[5] At the Floyd county line, US 18 and Iowa 27 become a limited-access road and angle slightly to the northeast, passing Rudd.

They intersect Iowa 14 on the western side of town and take a 90-degree curve to the east.

The two routes meet the northern end of Iowa 14, and US 18 splits away to the east to cross the Cedar River.

Heading east again, the route enters Chickasaw County and passes through Bassett on its way to New Hampton.

[5] Continuing due east, US 18 does not enter another community for 20 miles (32 km) until it reaches West Union in Fayette County.

The route turns to the northeast to through Clermont and then to the north to meet US 52 at Postville in southern Allamakee County.

Heading to the northeast toward McGregor and Marquette, its business loop goes through the towns while the mainline skirts around them.

The business loop rejoins the mainline at the foot of the Marquette–Joliet Bridge, which spans the Mississippi River.

[6] Before it and the rest of the U.S. Numbered Highway System were designated on November 11, 1926, US 18 was known by two names in the state.

[9] In seven years, the gap between O'Brien County and Algona was finished which created 160 miles (260 km) of continuous pavement.

During those same seven years, the route from West Union to the Mississippi River and all of Primary Road No.

That changed in when identical suspension bridges were built to cross the river between Marquette and Prairie du Chien, Wisconsin.

Built in 1931–1932, each bridge was 450 feet (140 m) long, crossed a main channel of the river, and were divided by a 2,000-foot-long (610 m) island causeway.