U.S. Route 64 (US-64) is a U.S. highway that passes through the state of Oklahoma for a total of 591.17 miles (951.40 km). US-64 enters the state from New Mexico, crossing the line between the two states between Clayton, New Mexico, and Boise City in Cimarron County. The route runs the full length of the Oklahoma Panhandle, then serves the northernmost tier of counties in the main body of the state before dipping southeastward to Tulsa, the state's second-largest city. From Tulsa, the highway continues southeast, leaving Oklahoma just west of Fort Smith, Arkansas. In addition to Tulsa, US-64 serves fifteen Oklahoma counties and the cities of Guymon, Woodward, Enid, and Muskogee. US-64 has been a part of the United States Numbered Highways system from the program's inception in 1926. US-64's route has remained roughly the same since then, although it has undergone alterations several times, many changing its course through towns and moving the highway designation to higher-capacity expressways and freeways.

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