U.S. Route 40 in the context of U.S. Route 66

U.S. Route 66 or U.S. Highway 66 (US 66 or Route 66) was one of the original highways in the United States Numbered Highway System. It was established on November 11, 1926, with road signs erected the following year. The highway ran from Chicago, Illinois, through Missouri, Kansas, Oklahoma, Texas, New Mexico and Arizona before terminating in Santa Monica, California, covering a total of 2,448 miles (3,940 km).

It was recognized in popular culture by both the 1946 hit song "(Get Your Kicks on) Route 66" and the Route 66 television series, which aired on CBS from 1960 to 1964. It was also featured in the Disney/Pixar animated feature film franchise Cars, beginning in 2006. In John Steinbeck's novel The Grapes of Wrath (1939), the highway symbolizes escape, loss and the hope of a new beginning; Steinbeck dubbed it the Mother Road. Other designations and nicknames include the Will Rogers Highway and the Main Street of America, the latter nickname shared with U.S. Route 40.

Interstate 64 (I-64) is an east–west Interstate Highway in the Eastern United States. Its western terminus is at I-70, U.S. Route 40 (US 40), and US 61 in Wentzville, Missouri. Its eastern terminus is at the Bowers Hill Interchange with I-264 and I-664 at Bower's Hill in Chesapeake, Virginia. I-64 connects Greater St. Louis, the Louisville metropolitan area, the Lexington–Fayette metropolitan area, the Charleston, WV metropolitan area, the Greater Richmond Region, and Hampton Roads.

Western Maryland, also known as the Maryland panhandle or Mountain Maryland, is the portion of the U.S. state of Maryland that typically consists of Washington, Allegany, and Garrett counties. The region is bounded by the Mason-Dixon line (Pennsylvania) to the north, the Potomac River and West Virginia to the south, and Preston County, West Virginia to the west. At one point, at the town of Hancock, the northern and southern boundaries are separated by just 1.8 miles (2.9 km), the narrowest stretch in the state.

Western Maryland is more rural than the Washington-Baltimore area, where most of the state's population lives, and is noted for its mountainous terrain. The area is in the central Appalachians. Washington, Allegany, and Garrett counties are part of the Appalachian Regional Commission. The most populous community in Western Maryland is Hagerstown, located in Washington County, the most populous county in the region. Major highways in Western Maryland include Interstate Highways I-70, I-81 and I-68; U.S. Highways U.S. 11, U.S. 40, U.S. 40 ALT, U.S. 219 and U.S. 50; and several state highways.

The Columbia metropolitan area is the region centered around the City of Columbia in the U.S. state of Missouri. Located in Mid-Missouri, it consists of five counties: Boone, Audrain, Randolph, Cooper, and Howard. The population was estimated at 256,640 in 2017, making it the 4th largest metropolitan area in Missouri. Columbia is home to the University of Missouri, and is Missouri's fourth most-populous and fastest growing city, with an estimated 121,717 residents as of 2017. Other significant cities in the area include Moberly, Mexico, Boonville, Vandalia, Centralia, and Fayette. There is also a 9-county Columbia–Jefferson City–Moberly combined statistical area with 415,747 residents.

The area was originally called the Boonslick and settled mainly by Kentuckians following the Boone's Lick Road starting around 1812. The town of Franklin, now washed into the Missouri River, was an early commercial center and start of the Santa Fe Trail. Columbia was founded as county seat of Boone County in 1821. The region was considered for the location of the Missouri State Capitol, but eventually a site was chosen 30 miles (48 km) south of Columbia and Jefferson City was created to serve that purpose. Today, Interstate 70, and U.S. Highways 63, 54, 24, and 40 link the urban areas. The U.S. census defines the Columbia MSA as Boone, Cooper, and Howard counties while the addition of the Jefferson City MSA along with Audrain and Randolph form the combined statistical area.