Headwaters of Empire explores how conflicting claims to sovereignty transformed Appalachian environments and shaped the exercise of state power in nineteenth-century North America. The expansion of U.S. empire into the Tennessee Valley coincided with a frenzy for state-building and new projects of republican governance. This dissertation shows that these competing claimants to sovereignty envisioned the creation of a governable and productive landscape in this region, which had a long history as a corridor for migration, trade, and warfare linking the Atlantic coast to the Mississippi Valley. Over the course of seventy years—roughly a single human lifetime—many groups, including Federal authorities; settlers and speculators; Cherokee nationalists; slaveholders and abolitionists; and Unionists and Confederates vied to control the land, what commodities it would grow, whose labor would work it, and who would profit from its transformation. Drawing on government records, military correspondence, surveys, and land office records, Headwaters of Empire maps these competing efforts to govern the nonhuman world, and explores the limits of state power in an environment hostile to its efficient operation. And through analyses of missionary records, family papers, newspapers, legal documents, and travelers’ accounts, it shows how local people responded to these claims to power in diverse ways, debating questions of sovereignty, nationhood, and their relationships with a more-than-human world. This dissertation reveals the creation of intersecting landscapes in the watersheds of the Tennessee and Coosa rivers— landscapes of state power that expanded the reach of coercive violence, and counter-landscapes of state evasion where the communities that bore the brunt of that violence maintained spaces of refuge and resistance. Exploring the ecological effects of settler colonialism across traditional boundaries of periodization in U.S. history, Headwaters of Empire also connects this local and regional story to hemispheric and global environmental histories that investigate how empire- making drove ecological change at a planetary scale in the nineteenth century and beyond.