The section between Mount Vernon and the southeast corner of Douglas County was Route 40 from 1922 to 1926.

Shortly after beginning it goes into an old alignment of US 60 making a sharp curve at McKinley.

It then heads east joining with (for one mile) U.S. Route 60 and Route 413 where it proceeds to pass through Clever and crosses the James River west of Nixa.

At the end of the concurrency it enters the Mark Twain National Forest and then passes through the hilly country of the Ozarks.

After those 52 miles it reaches its end at an intersection with US 63 at the northern boundary of West Plains.