The intersection with U.S. Highway 61 (US 61) in northern Muscatine marks the end of US 61 Bus.

[3] From Muscatine, Iowa 38 continues north eight miles (13 km) to the southern intersection with US 6 south of Wilton.

From I-80, the highway continues north towards Tipton where it meets the western end of Iowa 130.

Three-quarters mile (1.2 km) later, Iowa 38 meets and overlaps the former alignment of US 151, now US 151 Business.

At First Street, it leaves US 151 Bus to the west for a few blocks before turning north again towards Hopkinton and crossing the Maquoketa River.

Just north of Sand Springs, Iowa 38 intersects County Road X47 (CR X47), which is a cutoff to eastbound US 20.

Firstly, in 1932, it was extended over Iowa 117 for a couple miles and then north as a stub route to Center Junction.