U.S. Route 61 or U.S. Highway 61 (U.S. 61) is a major United States highway that extends 1,400 miles (2,300 km) between New Orleans, Louisiana and the city of Wyoming, Minnesota. The highway generally follows the course of the Mississippi River and is designated the Great River Road for much of its route. As of 2004, the highway's northern terminus in Wyoming, Minnesota, is at an intersection with Interstate 35 (I-35). Until 1991, the highway extended north on what is now Minnesota State Highway 61 (MN 61) through Duluth to the Canada–U.S. border near Grand Portage, then continued to Thunder Bay, Canada, as Ontario Highway 61. Its southern terminus in New Orleans is at an intersection with U.S. Route 90 (US 90). The route was an important south–north connection in the days before the interstate highway system.
The highway is often called the Blues Highway because of its long history in blues music; part of the route lies on the Mississippi Blues Trail and is denoted by markers in Vicksburg and Tunica. It is also the subject of numerous musical works, with the route inspiring the album Highway 61 Revisited by Bob Dylan.