Although technically a spur of US 18, US 218 neither begins nor ends at US 18, but overlaps US 18 for eight miles (13 km) near Charles City, Iowa.

US 218 begins at U.S. 136 in downtown Keokuk and ends 319 miles (513 km) away at Interstate 35 (I-35) and US 14 at Owatonna, Minnesota.

Prior to crossing the Skunk River, the roadway angles to the northeast and a freeway bypass of Mount Pleasant begins.

US 218 heads northwest through Vinton and La Porte City before it reaches the Waterloo area.

Route 218 remains a 2 lane highway until it becomes a freeway right before US 20 and once again joins I-380 for a couple miles to downtown Waterloo.

It continues northwest as a 4 lane highway through Waverly, Charles City, and Osage until the Minnesota state line.

It follows along the east side of the Iowa, Chicago, and Eastern Railroad line as it continues northward through farm fields.

Southeast of Austin, US 218 angles northeastward to bypass the city, its former route following County Road 45 (CR 45) into town.

When US 218 departs from the Interstate and turns back north, it becomes a four-lane divided highway for a short distance.

It continues north-northwesterly after leaving Blooming Prairie, traveling through predominantly agricultural scenery.

US 218 runs westward concurrently with US 14, while its historic route through downtown Owatonna continues ahead as CR 48.

It was called this because the original route was marked with poles which had red balls, six inches (150 mm) in diameter, mounted on each side.

In Iowa, US 218 was extended from its previous southern terminus, at its intersection with US 30 in Benton County, in 1934 when US 161 was split and renamed.

As the Eastern Iowa region has grown, traffic has increased, and the current arrangement of the interchange with its cloverleaf ramps has been deemed unsafe.