One segment of 26.97 miles (43.40 km) runs from Highway 96 north to Interstate 540 (I-540) in Fort Smith.

[4] A third segment of 25.42 miles (40.91 km) runs from College Avenue in Fayetteville north to Highway 12 west of Clifty.

[7] The route continues northeast through Clyde before passing the Pyeatte Mill Site and entering the historic community of Canehill.

Highway 45 runs through the Washington-Willow Historic District before a sharp left turn onto Mission Boulevard.

[1] The middle segment was replaced by Highway 59 between Van Buren and Dutch Mills, and the route remains fragmented today.