U.S. Route 80 or U.S. Highway 80 (US 80) is a major east–west United States Numbered Highway in the Southern United States, much of which was once part of the early auto trail known as the Dixie Overland Highway. As the "0" in the route number indicates, it was originally a cross-country route, from the Pacific Ocean to the Atlantic Ocean. Its original western terminus was at Historic US 101 in San Diego, California. However, the entire segment west of Dallas, Texas, has been decommissioned in favor of various Interstate Highways and state highways. Currently, the highway's western terminus is at an interchange with Interstate 30 (I-30) on the Dallas–Mesquite city line. Its eastern terminus is in Tybee Island, Georgia near the Atlantic Ocean. Between Jonesville, Texas and Kewanee, Mississippi, US 80 runs parallel to or concurrently with Interstate 20. It also currently runs through Dallas, Texas; Shreveport, Louisiana; Jackson, Mississippi; Montgomery, Alabama; Columbus, Georgia; Macon, Georgia; and Savannah, Georgia.

The system of auto trails was an informal network of marked routes that existed in the United States and Canada in the early part of the 20th century. Marked with colored bands on utility poles, the trails were intended to help travellers in the early days of the automobile.