U.S. Route 64 (US 64) is a U.S. highway running from the Four Corners area to the Outer Banks of North Carolina. Between these two points, the highway passes through the entire width of Oklahoma; a total of of US 64 lies in the state of Oklahoma. 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, mainly changing its course through towns and moving the highway designation to higher-capacity expressways and freeways.

Route description The Panhandle

U.S. Route 64 crosses the New Mexico–Oklahoma state line northeast of Clayton, New Mexico, concurrent with US 56 and US 412. The three highways enter the state just north of the extreme southwest corner of Cimarron County, the westernmost tip of the Oklahoma Panhandle. The highways head northeast, passing through disconnected parcels of the Rita Blanca National Grassland. The first town US 56, US 64 and US 412 encounter in Oklahoma is unincorporated Felt of which they skirt the northern edge. The highways then cross the Beaver River before intersecting US 385, which joins the other three highways in a concurrency as they approach Boise City, the county seat. In Boise City, the highways reach a traffic circle which surrounds the Cimarron County Courthouse. At this traffic circle, US 56, US 64 and US 412 all turn east while US 385 splits away to the north. State Highway 3 (SH-3) enters the circle from the north and leaves from the east, following US 64, while SH-325 begins at the circle and heads west toward Kenton. East of town, US 56/US 64/US 412/SH-3 have an interchange with US 287 which bypasses Boise City to the east. northeast of here, US 56 splits away from the other highways; it continues northeast, while US 64/US 412/SH-3 turn onto a due east course. The routes intersect SH-171 east of the split.

Approximately east of the SH-171 junction, US 64/US 412/SH-3 cross into Texas County. east of the county line, at unincorporated Four Corners, SH-95 joins the concurrency; it splits away after following the other three routes for . The next major highway junction lies to the east, where SH-136 joins with US 64/US 412/SH-3 as the highways turn south toward Guymon. The four highways cross the Beaver River once again before entering that city, Texas County's seat and the largest city in the Panhandle, on Main Street. In Guymon, US 64 splits away to the east along NE 12th Street, while US 412 and state highways 3 and 136 continue south. US 64 is accompanied on 12th Street by truck routes for the latter three highways. At the intersection with US 54, the truck routes turn southwest, while US 64 turns northeast, following US 54 out of town US 54/US 64 continue northeast through eastern Texas County, running parallel to a Union Pacific rail line. After crossing the Beaver River (the only crossing for US 54, but the third for US 64), the highways cut through the northwest corner of the town of Optima. Continuing northeast, US 54 and US 64 run just southeast of Panoma before coming to Hooker. There, US 54/US 64 serve as the northern terminus of SH-94. After the SH-94 junction, US 54 continues northeast toward Tyrone and Liberal, Kansas, while US 64 splits off onto a due east course. The road passes south of Baker before leaving Texas County.

Next, US 64 passes through Beaver County, the easternmost of the three counties forming the Oklahoma Panhandle. About east of the county line, US 64 reaches the town of Turpin; here, the highway begins a concurrency with US 83. Approximately north of Turpin, the two highways come to a junction with US 270. US 83 and westbound US 270 continue north from this junction toward Liberal, while US 64 and US 270 eastbound form a concurrency heading due east. Passing north of Floris, the highways proceed east for about without any curves or junctions with other highways before reaching Forgan. East of Forgan lies a highway junction with SH-23—here, US 270 splits away from US 64, turning south along SH-23 en route to the county seat, Beaver. SH-23 joins US 64 to form a concurrency before also splitting away toward its northern terminus at the Kansas line. US 64 does not intersect any other highways in the segment of highway in Beaver County east of the SH-23 junction. As it zig-zags southeastward, the highway passes through the towns of Knowles and Gate. east of Gate, the highway crosses the Beaver–Harper county line, the eastern boundary of the Oklahoma Pandhandle and enters the main body of the state.

Northern Oklahoma Just east of its entry into Harper County, US 412 begins a concurrency with US 283. The two highways pass through Rosston, then US 283 splits away to the south toward Laverne. US 64 continues alone on a due east course for before reaching the northern terminus of SH-46. The highway continues east, then veers northeast, and turns back to the east before meeting up with US 183 on the south side of Buffalo, the county seat. US 64 turns north at this intersection, overlapping US 183 through town. The two routes part ways northeast of town, with US 183 continuing on a northerly course toward Kansas and US 64 turning east once again. On the east end of the county, US 64 begins another concurrency, this time with SH-34. About east of the junction, the two highways cross the Cimarron River, which forms the northeastern boundary of Harper County.

As US 64 and SH-34 cross the Cimarron River, the two highways enter Woods County. SH-34 splits off to the north shortly thereafter. US 64 continues on east, passing through unincorporated Plainview and turning southeast to intersect SH-50 at its northern terminus at Camp Houston, north of Freedom. The next highway junction is just over east of Camp Houston, and is the northern terminus of SH-14 as signed; however, ODOT documents show SH-14 continuing east along US 64 from this point for slightly less than . The two highways proceed into the Woods County seat, Alva, where they join US 281. This concurrency lasts about before US 281 splits off to the north on the east side of town; at this point, SH-14 ends. US 64 continues east by itself for before reaching the eastern limit of Woods County.

The next county that US 64 serves on its path across Oklahoma is Alfalfa County. After passing through rural Alfalfa county, it approaches the unincorporated Ingersoll, whereupon it continues another until the route intersects state highways 8, 11 and 58. All three of these highways extend north from the intersection, while SH-11 continues east. US 64 turns south at this intersection, overlapping SH-8 and SH-58. They then pass through Cherokee, seat of Alfalfa County. About south of town, SH-8 splits away to the southwest, while US 64 and SH-58 turn due east. Approximately east of that intersection, SH-58 also splits away, headed south toward Helena. US 64 proceeds east to Jet, where it forms the southern terminus of SH-38. Four miles west of Jet, the highway exits Alfalfa County.

Upon leaving Alfalfa County, US 64 passes into Grant County. The first town the highway passes through in Grant County is Nash, where it begins a concurrency with SH-132. This concurrency lasts for before SH-132 splits away. east of this junction, US 64 intersects US 60 and US 81 in a T junction. US 81 northbound and US 60 eastbound continue straight, while US 64 eastbound turns south along with southbound US 81 and westbound US 60 (creating a wrong-way concurrency with US 60). The three highways continue south into Garfield County. south of the T junction, US 60 / US 64 / US 81 serve as the eastern terminus of SH-45. This junction marks the highways' entry into the Enid area. The highways serve as the city limit boundary between Enid (to the west) and North Enid (to the east). About south of the SH-45 junction, US 64 splits away from the other two highways at an interchange where US 64 continues south and US 60 / US 81 take a southwesterly tack. US 64 heads south from the interchange on North 4th Street. At Willow Road, US 64 turns due east; it follows Willow Road for about before turning south on North 30th Street. This street has a parclo interchange with Owen K. Garriott Road, which carries US 412; here, US 64 joins US 412 and the two highways head due east out of Enid as a four-lane expressway. East of Enid, the two routes pass between Breckenridge and Fairmont. South of Garber lies an interchange between US 64 / US 412 and SH-74. SH-15 also begins here, extending north along SH-74. US 64 / US 412 continue east out of Garfield County.

US 64 and US 412 next enter Noble County. The two highways' first junction with another highway in the county is a cloverleaf interchange at I-35 (exit 194 on the interstate). US 412 continues straight through the interchange, forming the Cimarron Turnpike, while US 64 follows I-35 southbound. US 64 splits away from the interstate in Perry at exit 186, heading due east, deeper into Perry. In downtown Perry, about east of I-35, US 64 has a brief concurrency with US 77. US 64 continues east out of Perry. West of Morrison, the highway crosses US 177. US 64 then passes through Morrison. East of town, US 64 has an interchange with the Cimarron Turnpike, still carrying US 412, at turnpike exit 22. US 64 continues northeast to Lela, where it serves as the northern terminus of SH-108, which runs along the Noble–Pawnee county line. US 64 continues east into Pawnee County.

About into Pawnee County, US 64 enters the county seat, Pawnee. Here, the route begins a concurrency with SH-18. The two highways head southeast out of town together for just over before SH-18 splits off to the south toward Lone Chimney. US 64 continues alone to the east for about before beginning another concurrency, this time with SH-99 on the outskirts of Cleveland. The two highways leave Cleveland, proceeding east through unincorporated territory, before re-entering the city. Here, the two highways head in separate directions, with SH-99 heading north and US 64 heading southeast. This portion of the highway runs parallel to Keystone Lake, a reservoir formed by the impounded Arkansas River. US 64 intersects with SH-48 at the latter's northern terminus before merging with US 412 in a partial interchange (the missing movements are provided via SH-48). This interchange is also the Cimarron Turnpike's eastern endpoint.

Tulsa area US 64 / US 412 continue east from the eastern terminus of the Cimarron Turnpike in southeastern Pawnee as a freeway known as the Keystone Expressway. This highway continues eastward along a peninsula into Lake Keystone. Here, the highway serves as the southern limit of Westport and Mule Barn, which remains an incorporated town despite having a population of zero. The freeway turns southeast, briefly entering Westport before crossing Lake Keystone into Osage County. US 64 and US 412 run through Osage County for just under , cutting across a corner of the county before entering Tulsa County.