Route 125 runs between U.S. Route 65 at Fair Grove and the Arkansas state line, where it continues as Highway 125.

After the road crosses into Marion County, Arkansas, the highway crosses Bull Shoals Lake via a free ferry.

Near Chadwick, the highway enters the Mark Twain National Forest and passes through this most of the way to Arkansas.

The roads ends at U.S. Route 65 at Fair Grove and the road continues as Missouri Route CC.

From its northern terminus at Fair Grove the highway passes through eastern Greene County, northern and southeastern Christian County and eastern Taney County.