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. 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 also overlaps U.S. Route 160 for several miles at Rueter. It overlaps Route 14 through most of Sparta. It crosses US 60 near Rogersville. It cross I-44 near Strafford, Missouri. 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.

County	Location	mi	km	Destinations	Notes
Taney	​	0.000	0.000	AR 125	Continuation into Arkansas
	​	9.879	15.899	US 160 east	Southern end of US 160 overlap
	​	11.829	19.037	US 160 west	Northern end of US 160 overlap
	​	27.114	43.636	Route 76 west	Southern end of Route 76 overlap
	Bradleyville	27.780	44.708	Route 76 east	Northern end of Route 76 overlap
Christian	Sparta	51.331	82.609	Route 14 east	Southern end of Route 14 overlap
		52.051	83.768	Route 14 west	Northern end of Route 14 overlap
Greene	Rogersville	62.053	99.865	US 60	Roundabout interchange
	Strafford	73.955	119.019	I-44	I-44 exit 88
	Fair Grove	83.556	134.470	US 65 / Route CC	Interchange; Roadway continues as Route CC
1.000 mi = 1.609 km; 1.000 km = 0.621 mi       Concurrency terminus