Route 125 runs between U.S. Route 65 at Fair Grove and the Arkansas state line, where it continues as Highway 125. It is a two-lane road its entire length. Near Chadwick, the highway enters the Mark Twain National Forest and passes through this most of the way to Arkansas. It overlaps Route 14 through most of Sparta. It also overlaps U.S. Route 160 for several miles at Rueter. After the road crosses into Arkansas, the highway crosses Bull Shoals Lake via a free ferry.