The history of the Southern United States reaches back hundreds of years and includes the Mississippian people, well known for their mound building. European history in the region began in the very earliest days of the exploration and colonization of North America. Spain, France, and England eventually explored and claimed parts of what is now the Southern United States, and the cultural influences of each can still be seen in the region today. In the centuries since, the history of the Southern United States has recorded a large number of important events, including the American Revolution, the American Civil War, the ending of slavery, and the American Civil Rights Movement.

In Pre-Columbian times, the only inhabitants of what is now the Southern United States were Native Americans. The most important Native American nation in the region was the Mississippian people, who were a Mound builder culture that flourished in the Midwestern, Eastern, and Southeastern United States in the centuries leading up to European contact. The Mississippian way of life began to develop around the 10th century in the Mississippi River Valley (for which it is named).