U.S. Route 61 is the official designation for a United States highway that runs 1,400 miles from New Orleans, Louisiana, to the city of Wyoming, Minnesota. As of 2004, the highway's northern terminus in Wyoming, Minnesota, is at an intersection with Interstate 35. Prior to 1991, the highway extended north through Duluth, Minnesota to the United States-Canada border near Grand Portage, Minnesota. Its southern terminus in New Orleans is at an intersection with U.S. Highway 90 (Tulane Avenue at South Broad Street).

The route was an important north-south connection in the days before the interstate highway system. Many southerners traveled north along Highway 61 to go to St. Louis.