This session presents a broad spectrum of geographical, cultural, and historical comparisons across early modern Ibero-America from the northern borderlands of New Spain (colonial Mexico) through two Mesoamerican cultural spheres of central New Spain, to one of the major Indigenous/Portuguese borderlands of Brazil. Its unifying themes meet in the cutting-edge scholarship that addresses different forms of Indigenous knowledge, and the ways in which it became central to imperial governance, the development of colonial societies, and the survival of Indigenous communities and lifeways in the Americas. Knowledge, as employed here, can encompass medical/botanical knowledge, close familiarity with the geography of a given region, or strategic knowledge that Indigenous peoples used to negotiate with Spanish or Portuguese interlocutors. Justyna Olko structures her paper, “Place-based knowledge, acculturation, and resilient ecologies,” around the centuries-long documented histories of the defense of land, forests, and water ways by the Tlaxcallan city-states and villages of central Mesoamerica. It shows their assertion of extensive environmental knowledge of the territory they claimed – and continue to defend – among the Nahua-speaking peoples of Mexico. Co-authors Omar Aguilar Sánchez and Izaira López Sánchez, both Ñuu Savi (Mixtec) scholars, bring to light the religious meanings inherent in colonial mapping for Indigenous peoples who defended their lands before Spanish authorities. Their presentation, “Mixtec Colonial Maps as Sacred Landscapes,” interprets early colonial Mixtec códices in terms not only of their legal import, but also in the light of present-day religious practices deeply linked to the sacred quality of landscapes within the Mixteca Alta of Oaxaca. Turning to the borderlands of Spain’s vast northern territories, José Manuel Moreno Vega captures the complexities of interethnic relations among different Indigenous peoples and Hispanocriollos. In “Knowledge was their Main Asset,” Moreno Vega focuses on the testimony of an Apache captain of the Gila river valley, transported far from his homeland to the viceregal capital of Mexico City in the late eighteenth century. Moreno Vega presents this case to show how Indigenous knowledge can be found and analyzed in primary sources as a resource or “asset” that Indigenous actors used in dealing with both secular and ecclesiastical colonial authorities. Elaborating on a similar theme for eighteenth-century Brazil, Hal Langfur’s paper, “All that Glitters: Native Knowledge and Regal Dreams in Southeastern Brazil,” explores the limits of colonial authority and the “contested mastery of backcountry geographic and strategic knowledge” in the tropical Atlantic rainforests of Brazil. The panel discussant, Barbara Ganson, is a recognized scholar of Guaraní history and cultural legacies in Paraguay and the greater Río de la Plata. Taken together, the session represents diversity in the academy through a strong collaboration among four well established scholars with two of the presenters, the discussant, and the organizer and chair, and three young scholars who are beginning to find publishing outlets for their work and demonstrate innovative interdisciplinary approaches to the production of historical knowledge. In addition, all the participants bring to this session a diversity of academic institutions, linguistic backgrounds, and national traditions.