It runs for 912 miles (1,468 km) from St. John, Indiana, at US 41 to south of US 98 in downtown Panama City, Florida.

Continuing north, US 231 passes through Youngstown, Fountain, Alford, Cottondale, and Campbellton before entering Alabama.

Through Huntsville, Alabama, the route functions as Memorial Parkway - the main north-to-south freeway through downtown.

About a mile north of the second junction with US 72, the route loses its frontage roads and reverts to a four-lane divided highway.

In general, the route is an important connector between Dothan, Montgomery, and Huntsville, three of the most populous cities in the state.

By the time it reaches Bethpage, it joins U.S. Route 31E in another concurrency to the northeast before finally crossing the Kentucky State Line north of Westmoreland.

At Owensboro, US 231 joins US 60 (also known as the Wendell H. Ford Expressway) around the city's east side, which it then follows to just north of Maceo.

As part of this program, US 231 is currently being updated to a new-terrain four-lane highway from the Indiana-Kentucky border through Spencer County to Interstate 64.

As of April 2011, the Lincoln Parkway is complete from the Kentucky line to the interchange at I-64 and the bypass of Dale at the northernmost end of the project.

The section from SR 162 to Indiana State Highway 70 near Chrisney was the last to be opened, after a ribbon-cutting ceremony on March 15, 2011, much sooner than the original July 2011 projected date.