The Unsettlement of America explores the career and legacy of Don Luis de Velasco, an early modern indigenous translator of the sixteenth-century Atlantic world who traveled far and wide and experienced nearly a decade of Western civilization before acting decisively against European settlement. The book attends specifically to the interpretive and knowledge-producing roles played by Don Luis as a translator acting not only in Native-European contact zones but in a complex arena of inter-indigenous transmission of information about the hemisphere. The book argues for the conceptual and literary significance of unsettlement, a term enlisted here both in its literal sense as the thwarting or destroying of settlement and as a heuristic for understanding a wide range of texts related to settler colonialism, including those that recount the story of Don Luis as it is told and retold in a wide array of diplomatic, religious, historical, epistolary, and literary writings from the middle of the sixteenth century to the middle of the twentieth. Tracing accounts of this elusive and complex unfounding father from the colonial era as they unfolds across the centuries, The Unsettlement of America addresses the problems of translation at the heart of his story and speculates on the implications of the broader, transhistorical afterlife of Don Luis for the present and future of hemispheric American studies.