Among the Native American tribes to have called what is now Louisiana home were the Atakapa, the Caddo Confederacy, Chitimacha, Choctaw, Natchez, and Tunica. As well, the Watson Brake site near what is near Monroe is the oldest mound complex in North America.

Spanish explorers coming north from the mouth of the Mississippi River visited in what is now Louisiana in 1528. Famed Spanish explorer Hernando de Soto moved through the area in 1541, on his way to lands farther and farther away from Spain. Theirs was more of an exploratory mission, and it not until more than a century later that a permanent European settlement appeared.

The famous French explorer RenéRobert Cavelier, de La Salle arrived in 1682 and, claiming the area for France, named it La Louisiane for his king, Louis XIV.

The oldest European settlement in Louisiana was established in 1714 at Natchitoches, on the Red River. The city of New Orleans began in 1718, founded by Jean Baptist Le Moyne in order to take full advantage of the excellent port conditions there. Biloxi and Mobile were capitals of this French colony at one point. New Orleans became the capital in 1722, just a couple of years after the establishment of a German settlement along the Mississippi River. (This was known as the German Coast settlement.)

The Louisiana Territory grew and grew and eventually came to include what is now Arkansas, Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Mississippi, Missouri, Nebraska, North Dakota, Oklahoma, South Dakota, and Wisconsin.

The British victory over France in the French and Indian War in 1763 resulted in French transfer of all lands east of the Mississippi River to Great Britain and of New Orleans to Spain.

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