Indigenous communities thrive in the Southeast, including ancestors of what would become the Cherokee, Chocktaw, Chickasaw, Seminole, and Creek tribes.

The Spanish, French, and British all arrive to and colonize the South. Juan Ponce de Leon lands in Florida in 1513; the French settle in what is now Jacksonville, Florida in 1562; and in 1585, Sir Walter Raleigh establishes the first British settlement in what is now North Carolina.

Tobacco is introduced as a crop and becomes an important part of the Southern economy.

The first enslaved Africans were brought to Virginia. As plantations grew in the South, slavery would become the basis for the Southern economic and social system.

Eli Whitney invents the cotton gin and cotton becomes an important crop in the South.