A current goal among many scientific disciplines is to incorporate data on past human land use and climate change into current global climate and vegetation models. Here, we used existing archaeological and paleoecological data to provide a spatiotemporal reconstruction of human history in Greater Amazonia over the Holocene. We used an ensemble distribution model based on a database of georeferenced 14C-dated material and environmental factors to predict the changes in spatial distributions of past human occupation sites. We ran these models for the precultivation (13,000–6000 yr ago), early cultivation (6000–2500 yr ago), and late cultivation (2500–500 yr ago) periods. The ensemble models suggest that people mostly inhabited the peripheral areas of Greater Amazonia and the eastern sections of the main Amazon River and its larger tributaries during the precultivation period. Human populations began growing exponentially through the early cultivation period, and people spread and expanded into the interior forests and along river channels in western Amazonia. Populations continued growing through the late cultivation period in these same regions. Our results suggest that many forests, particularly in the peripheral regions and riverine locations, may still be in recovery from disturbances that have occurred repeatedly through the Holocene.