US 64's western terminus is Teec Nos Pos, Arizona, at US 160. From there, it runs southeast through sparse ranch land for about 4.16 miles (6.69 km) to the New Mexico state line.
New Mexico
Within New Mexico, US 64 runs through Farmington, Taos, Angel Fire, Eagle Nest, Cimarron, and Raton. As it runs through Raton, it is co-signed with U.S. Route 87. It continues through to Clayton, where US 87 is replaced by U.S. Routes 56 and 412. The three routes then run concurrently into Oklahoma.
Although US 64 does not technically cross into Texas, the New Mexico-Texas border does reach the shoulder of US 64 outside of Clayton at 36°30′01″N 103°02′31″W / 36.500352°N 103.041922°W / 36.500352; -103.041922.
Oklahoma
Heading into the Oklahoma Panhandle, the three conjoined routes pick up a fourth two miles (3 km) southwest of Boise City, as US-385 merges from the south. In Boise City, US-385 departs to the north along with U.S. 287, which replaces US-385 in the four-way concurrency on the way out of town to the east, before departing itself to the southeast two miles (3 km) outside of town. Shortly thereafter, US-56 also departs the route, heading northeast into Kansas, while US-64 and US-412 continue their journey due east toward Guymon.
Near Guymon, the route turns due south to approach the town. US-412 then heads due east, while US-64 veers from due south to northeast, joining up with US-54. These two routes remain together for about 20 miles (32 km), splitting at Hooker, with US-54 continuing northeast into Kansas while US-64 again veers due east. At Turpin, US-64 turns left, running north with US-83; three miles (5 km) later, it again turns east, joining US-270 while US-83 and westbound US-270 continue north to Liberal, Kansas. Twenty miles (32 km) to the east, US-270 departs to the south, and US-64 finally runs solo for a significant stretch save for very short concurrencies with US-283 near Rosston, US-183 through Buffalo, and US-281 in Alva.
Near Pond Creek, US-64 turns south, joined by US-60 and US-81. US-64 splits off just north of Enid, jogging through the city before rejoining US-412 on the east side of town. The two routes remain together until they meet Interstate 35, which US-64 joins briefly southbound while US-412 continues east, becoming the Cimarron Turnpike. US-64 departs I-35 at Perry, intersecting the parallel US-77 before continuing east.
On either side of Morrison the route intersects US-177 and US-412 (again) before passing through Pawnee and Cleveland. It then veers southeast, rejoining US-412 yet again to head into Tulsa.
In downtown Tulsa, the route diverges from US-412 for the final time. It briefly (and separately) is concurrent with Interstate 244 and US-75 before bearing southeast through the city while joining OK-51, intersecting Interstate 44 before briefly joining the southernmost five miles (8 km) of US-169, disjoining OK-51 running southbound on the eastern edge of the city. It then proceeds south, crossing the Creek Turnpike, then crosses the Arkansas River in Bixby before turning to the southeast.
After passing through Haskell, US-64 and US-62 meet head-on, north–south; they join and head east toward Muskogee. The routes disengage at the intersection with US-69, with US-64 bearing south out of the center of town. At Warner, the route turns eastward again, where it will run parallel to Interstate 40 for the remainder of its path through Oklahoma. It passes through Webbers Falls, Gore, Vian, Sallisaw (where it has a brief concurrence with US-59), Muldrow, and Roland before leaving the state.
US 64 enters Tennessee on the Memphis-Arkansas Bridge at Memphis. The route shares the bridge with Interstate 55 and U.S. Routes 61, 70, and 79. The route traverses several streets in Memphis before becoming a rural divided highway in eastern Shelby County. The highway runs directly to the east through the county seats of Tennessee's most southern counties. US 64 then continues on past Lawrenceburg, the largest city on the Alabama state line between Memphis and Interstate 65, to Chattanooga. Then US 64 runs from Chattanooga to Cleveland, where it duplexes with US 74 to the North Carolina state line. The Tennessee Department of Transportation is currently working to expand the highway to four lanes across the state. The easternmost portion of the highway in Tennessee is the Ocoee Scenic Byway, a winding, two-lane road through the Ocoee Rivergorge in Polk County. The steep terrain around the highway is subject to landslides, such as the massive slide in November 2009 that closed the highway for several months.[2]
The segment from Franklin to Highlands is a mountainous two-lane road limited to moderate-sized trucks. Large trucks are routed via Truck US 64 (US 23/441 and US 74) to Sylva, and Asheville.
Interstate 40 travels through Statesville on a route originally designed in 1950 as a bypass of US 64, intersecting with Interstate 77 at what was once intended to be a bypass of US 21.
Within the Raleigh city limits, US 64 follows the southern section of the Beltline. In 2006 a major section known as the Knightdale Bypass opened to ease traffic. After it was completed, US 64 became a divided freeway between Cary and Williamston, and carried at least four lanes between Asheboro and Columbia.
US 64 extends a total of 563 miles (906 km) from the state's western border to the Outer Banks. It is the longest highway in North Carolina; a common way to express coverage of the entire state is to say, "from Murphy to Manteo". US 64 runs through both.
I-40 / US 63 / US 79 in West Memphis. I-40/US 64 travels concurrently through West Memphis. US 64/US 79 travels concurrently to the Memphis–Bartlett, Tennessee city line.
US 70 in West Memphis. The highways travel concurrently to the Memphis–Bartlett, Tennessee city line.
I-40 / I-440 in Raleigh. I-440/US 64 travels concurrently through Raleigh.
I-87 / I-440 / US 264 in Raleigh. I-87/US 64 travels concurrently east from I-440 to Rolesville Road in Wendell. Future I-87 is slated to continue concurrently with US 64/US 264 in the near future.
There are several sections of Business US 64 serving more as alternate routes of the main highway. While they go through towns and cities, they often run numerous miles through rural areas and often pass through more than one city.