U.S. Route 51 or U.S. Highway 51 is a major south–north United States highway that extends 1,277 miles (2,055 km) from the western suburbs of New Orleans, Louisiana, to within 150 feet (46 m) of the Wisconsin–Michigan state line. As most of the United States Numbered Highways ending with "1", it is a cross-country north–south route extending from the Gulf Coast region to the Great Lakes region. Much of the highway in northern Illinois and southern Wisconsin runs parallel to or is cosigned with Interstate 39 (I-39) and much of the route in several states also parallels the Illinois Central Railroad. From LaPlace, Louisiana, Mississippi, to Memphis, Tennessee, much of that portion of US 51 runs largely parallel or is concurrent with Interstate 55 (I-55). The highway's northern terminus is between Hurley, Wisconsin, and Ironwood, Michigan, where it ends with a roundabout at US 2. Its southern terminus is in Laplace, Louisiana, ending at US 61. US 51 is routed through the states of Louisiana, Mississippi, Tennessee, Kentucky, Illinois, and Wisconsin.

The Gulf Coast of the United States, also known as the Gulf South or the South Coast, is the coastline along the Southern United States where they meet the Gulf of Mexico. The coastal states that have a shoreline on the Gulf of Mexico are Texas, Louisiana, Mississippi, Alabama, and Florida, and these are known as the Gulf States.