U.S. Route 64 is a major east–west highway spanning approximately 2,300 miles across the southern and central United States. It begins in the scenic Outer Banks of North Carolina at Whalebone Junction and stretches westward all the way to the Arizona border in northeast New Mexico, just east of the town of Teec Nos Pos. Along its path, US 64 passes through a diverse array of landscapes, including coastal plains, the Appalachian Mountains, fertile farmland, and desert mesas.

The highway serves as a vital connector through six states: North Carolina, Tennessee, Arkansas, Oklahoma, New Mexico, and a brief portion of eastern Arizona. In the eastern states, US 64 closely parallels major interstates like I-40 but often provides a more scenic or locally accessible alternative. In the west, especially through Oklahoma and New Mexico, it cuts through rural areas and tribal lands, including a picturesque stretch through the Cimarron Canyon and the Sangre de Cristo Mountains.

U.S. Route 64 intersects with numerous important routes, including I-75 in Tennessee, I-35 in Oklahoma, and US 285 in New Mexico. Its role as a regional thoroughfare is enhanced by its proximity to natural and cultural attractions such as the Great Smoky Mountains, Memphis, the Ozarks, and Taos. This blend of utility and charm makes US 64 a favorite for both long-haul drivers and road-tripping travelers seeking a less-traveled path across the heart of America.