Its southern terminus is at the Arkansas state line in downtown Blue Eye, Missouri–Arkansas where it continues as Highway 21.

Several sections from north of Reeds Spring through Branson West have been widened, rebuilt, moved, and renamed to help ease traffic congestion through the towns.

Drivers regularly use these routes to get to many of the lakes in southern Missouri and this has caused a major headache in recent years.

[1] In 2006 the portion through Caldwell County, Missouri was named the Zack Wheat Memorial Highway in honor of the Baseball Hall of Fame player.

[1] Archived June 27, 2007, at the Wayback Machine Route 13 begins at the Arkansas state line in Blue Eye.

After leaving the town, it travels through the rugged countryside of the southwest Missouri Ozarks, part of the Mark Twain National Forest.

The two highways continue north into Greene County, where they enter Springfield traveling along Campbell Avenue.

It then passes near the Ozark Empire Fairgrounds and the Dickerson Park Zoo and leaves the city as a divided highway.

A project begun in 2009 and completed on June 21 of that year, turned the existing I-44 interchange into a diverging diamond, which was the first of its kind in the nation.

In addition to costing $2.5 million compared to around $8 million for a complete rebuild, this has also helped ease congestion at the interchange by making lefts onto the on-ramps "free lefts" by lanes shifting into opposite lanes when passing over the bridge.

From US 24 in Lexington to the intersection with Route 10 in Richmond, the highway is a four-lane limited access road.