This dissertation conceptualizes “native information” as both an object of governance and a process of engagements between the original inhabitants of the western hemisphere and European colonists that prefigures and produces an indigenous subject. I demonstrate this through a study of the period of colonization in the western hemisphere between the years 1492 and 1688, and the impact of colonization in the western hemisphere on the knowledge produced in the course of the late Renaissance and early Scientific Revolution. I focus especially on the interactions between the Taino and Inca and the Spanish, and also between the Roanoke and Catawba and the British during this period to illustrate my argument. Native information emerged in this context through debates over four overlapping elements that were said to characterize indigenous subjects in the Americas: Difference, Nature, Vernacular Histories, and Proprietary Identities. Native information was collected from the original inhabitants of the western hemisphere, and was curated by colonial agents so as to speak to these concerns in the late Renaissance and early Scientific Revolution. In turn, the political and legal categories that European scholars of this period developed on the basis of native information came to define and circumscribe the terms of life and death for the original inhabitants of the western hemisphere under the increasing pressure of growing colonial occupation. However, not all information with which European colonists and intellectuals were presented was treated as equally relevant. Consequently, those points where either native information was refused by Europeans or where Europeans’ attempts to enforce the indigenous status that the former claimed to flow directly from native information were sites in which the original inhabitants of the western hemisphere critically highlighted the contradictions, limits, and violences of colonial governance and its attendant systems of thought in ways that confound the indigenous subjects colonists both imagined and sought to produce.