At no point along its route is Iowa 2 more than 15 miles (24 km) from the Missouri state line, except for a small section near its eastern terminus.

It continues east through New Market and meets Iowa Highway 148 at Bedford.

After passing through Kellerton, Iowa 2 intersects Interstate 35 at Decatur City.

After passing through Promise City, it goes through Centerville, where it intersects Iowa Highway 5.

From there, it then meets U.S. Highway 61 and ends on the west side of Fort Madison.

3 was overlaid upon the Waubonsie Trail from the Missouri River to Fort Madison.

From Fort Madison, it overlapped the Mississippi Valley Scenic Highway, a precursor to the Great River Road.