One route begins at Salmon Lane in Boone County and runs 1.63 miles (2.62 km) north to US Highway 65 Business (US 65B) in Harrison.

A second route begins at Highway 103 in Clarksville and runs 67.74 miles (109.02 km) northeast to US 65 and US 65B in Western Grove.

The route begins at Salmon Lane south of Harrison and west of Bellefonte in Boone County.

[3] As of 2016, the route had an annual average daily traffic (AADT) of 600 vehicles per day (VPD).

The route is one of the few north–south corridors in the dense and sparsely populated forest, and passes many campsites, rivers, and hiking trails for recreational use.

It runs east past Johnson Regional Medical Center and the historic Pioneer House before entering Lamar, where it overlaps US 64.

North of Hagarville, the route enters the Ozark National Forest, becoming a winding rural road.

[9] The routes begin an overlap northbound, passing the Thomas J. Hankins House, listed on the National Register of Historic Places.

Highway 123 continues north, passing through the western side of the Gene Rush WMA and crossing the Buffalo National River near Carver Day Use Area, a river landing and campsite maintained by the National Park Service (NPS).