State Highway 66 is a 192.7-mile (310.1 km) state highway in the U.S. state of Oklahoma, beginning at U.S. Highway 81 in El Reno and ending at U.S. Highway 60 near White Oak. The highway was designated in 1985 as a replacement for the decommissioned U.S. Highway 66. Although most of the highway follows Historic Route 66, the highway follows US 66's final alignment, joining Interstate 44 through Tulsa and Oklahoma City, while older versions of the route follow various city streets through both cities.

U.S. Route 81 (US-81) is a north–south U.S. highway running through the central United States' Great Plains region, from Fort Worth, Texas to the U.S.–Canadian border at Pembina, North Dakota. A 229.28-mile (368.99 km) segment of the highway lies within the state of Oklahoma. US-81 crosses the Red River from Texas south of Terral, passing through several Oklahoma cities, such as Chickasha, El Reno, Kingfisher, and Enid, before entering Kansas north of Renfrow.