Interstate 40 (I-40) is a major east–west transcontinental Interstate Highway in the southeastern and southwestern portions of the United States. At a length of 2,556.61 miles (4,114.46 km), it is the third-longest Interstate Highway in the country, after I-90 and I-80. From west to east, it passes through California, Arizona, New Mexico, Texas, Oklahoma, Arkansas, Tennessee, and North Carolina. Its western terminus is at I-15 in Barstow, California, while its eastern terminus is at a concurrency with U.S. Route 117 (US 117) and North Carolina Highway 132 (NC 132) in Wilmington, North Carolina. Major cities served by the Interstate include Flagstaff, Arizona; Albuquerque, New Mexico; Amarillo, Texas; Oklahoma City, Oklahoma; Fort Smith and Little Rock in Arkansas; Memphis, Nashville, and Knoxville in Tennessee; and Asheville, Winston-Salem, Greensboro, Durham, Raleigh, and Wilmington in North Carolina.

I-40 begins in the Mojave Desert in California, and then proceeds through the Colorado Plateau in Arizona and the southern tip of the Rocky Mountains in New Mexico. It then traverses the Great Plains through the Texas Panhandle and Oklahoma, and passes south of the Ozarks in Arkansas. The freeway crosses the Appalachian Mountains in Tennessee and North Carolina, before terminating in the Atlantic Coastal Plain near the Atlantic Ocean.

Much of the western part of I-40, from Barstow to Oklahoma City, parallels or overlays the historic U.S. Route 66. East of Oklahoma City, the route generally parallels US 64 and US 70. I-40 was established by the Federal-Aid Highway Act of 1956, and the numbering was subsequently approved on August 14, 1957, along with most of the rest of the system. The eastern terminus was initially planned to be located at I-85 in Greensboro, but the Federal Highway Administration later approved extending the route to its current eastern terminus in Wilmington. As a result, this was the last segment of I-40 to be completed upon its dedication in 1990.

I-40 is the third-longest freeway in the United States, spanning 2,556.61 miles (4,114.46 km) across the southern half of the country. The longest stretch of the highway is in Tennessee, and the shortest is in California. The busiest stretch of I-40 is in Knoxville, concurrent with I-75, which has an annual average daily traffic volume of more than 210,000 vehicles. The lowest traffic volumes are found on rural stretches in New Mexico, Texas, and Oklahoma, where the freeway carries fewer than 15,000 vehicles per day.

I-40 in California crosses through the lightly populated northern part of the Inland Empire region of the state. Its western end is in Barstow, California. Known as the Needles Freeway, it heads east from Barstow across the Mojave Desert in San Bernardino County to Needles, before it crosses the Colorado River into Arizona southwest of Kingman. I-40 covers 155 miles (249 km) in California. Some signs show the control city for I-40 westbound to be Los Angeles, where drivers would follow I-15 south from its western terminus in Barstow. The highway is four lanes for the entirety of its length in the state.

A sign in California showing the distance to Wilmington, North Carolina, has been stolen several times.

I-40 is a main route to the South Rim of the Grand Canyon, with the exits leading into Grand Canyon National Park in Williams and Flagstaff. I-40 covers 359 miles (578 km) in Arizona. Just west of exit 190, west of Flagstaff, is its highest elevation along I-40 in the US, as the road crosses just over 7,330 feet (2,230 m) at the Arizona Divide near milepost 190. I-40 also passes through the Navajo Nation, the largest Indian reservation in the US. Like California's segment, the highway is four lanes for the entirety of its length in the state.

I-40 covers 374 miles (602 km) in New Mexico. As in other states it parallels or overrides the post 1937 Route 66 route through the state. Notable cities along I-40 include Gallup, Grants, Albuquerque, Santa Rosa, and Tucumcari. I-40 also travels through several Indian reservations in the western half of the state. It reaches its highest point in the state of 7,275 feet (2,217 m) at the Continental Divide (Campbell Pass) in western New Mexico between Gallup and Grants. The last place that I-40 tops 7,000 feet (2,100 m) is at the head of Tijeras Canyon east of Albuquerque at approximately 7,040 feet (2,150 m).