How did the Native South become the Deep South within the span of a single generation? This dissertation argues that these ostensibly separate societies were in fact one and the same for several decades. It significantly revises the history of the origins of antebellum America’s slave-based economy and shows that the emergence of a plantation society in Alabama and Mississippi was in large part a grassroots phenomenon forged by Indians and other native inhabitants as much as by Anglo-American migrants. This native transformation occurred because of a combination of weak European colonial regimes, the rise of cattle, cotton, and chattel slavery in the region, and the increasingly complex ethnic and racial geography of the Gulf South. Inhabitants of the Gulf South between the American Revolution and Indian removal occupied a racial and social milieu that was not distinctly Indian, African, or European. Nor can it be adequately defined by hybridity. Instead, Gulf southerners constructed something unique. Indians and native non-Indians—white and black—owned ranches and plantations, employed slave labor, and pioneered the infrastructure for cotton production and transportation. Scotsmen and Spaniards married Indians and embraced their matrilineal traditions. Anglo- and Afro-American migrants integrated into an emergent native cotton culture in which racial and cultural identities remained permeable and flexible. Thus, colonial and borderland-style interactions persisted well into the nineteenth century, even as the region grew ever more tightly bound to an expansionist United States. The history of the Gulf South offers a perfect opportunity to bridge the imagined divide between the colonial and early republic eras. Based on research in multiple archives across five states, my work thus alters our understanding of the history and people of an American region before the Civil War and reshapes our framework for interpreting the nature of racial and cultural formation over the long course of American history.