It extends the corridor formed by U.S. Route 75 in Texas, from Dallas northeast via McAlester and Muskogee to the Will Rogers Turnpike (Interstate 44) near Vinita.

U.S. Highway 69 crosses the Red River to enter Bryan County, Oklahoma concurrent with US-75 3 miles (4.8 km)[2] south of Colbert.

The freeway continues northeast, providing access to Armstrong, Caddo, and SH-22 before becoming an expressway once again at the Atoka County line.

North of this interchange, US-75 and SH-3 split off, leaving US-69 without any concurrent routes for the first time since crossing the Red River.

US-69 then heads through unincorporated Chockie, and then serves as the eastern terminus of SH-131 just south of the Pittsburg County line.

US-69 runs along the east edge of the McAlester Army Ammunition Plant, which it provides access to via an interchange near Savanna.

[further explanation needed] US-69 meets the western terminus of State Highway 165 as it enters Muskogee.

The route runs along the west side of the city, intersecting U.S. Highway 64 and briefly concurring with US-62.

[2] US-60/69 cut the northwest corner of Delaware County, entering just west of the northern terminus of State Highway 85.

The two routes concur briefly before splitting near downtown Miami, where US-69 forms a one-way couplet.

The main route turns north, running through the Tar Creek Superfund site and abandoned community of Picher, before leaving Oklahoma and entering the state of Kansas.