We test the hypothesis that prehistoric Native American land use influenced the Euro-American settlement process in a South Carolina Piedmont landscape. Long term ecological studies demonstrate that land use legacies influence processes and trajectories in complex, coupled social and ecological systems. Native American land use likely altered the ecological and evolutionary feedback and trajectories of many North American landscapes. Yet, considerable debate revolves around the scale and extent of land use legacies of prehistoric Native Americans. At the core of this debate is the question of whether or not European colonists settled a mostly "wild" landscape or an already "humanized" landscape. We use statistical event analysis to model the effects of prehistoric Native American settlement on the rate of Colonial land grants (1749-1775). Our results reveal how abandoned Native American settlements were among the first areas claimed and homesteaded by Euro-Americans. We suggest that prehistoric land use legacies served as key focal nodes in the Colonial era settlement process. As a consequence, localized prehistoric land use legacies likely helped structure the long term, landscape- to regional-level ecological inheritances that resulted from Euro-American settlement.