A multi-proxy paleo-data synthesis of 110 sites is presented, exploring the impact of mid- to late Holocene precipitation changes upon vegetation across Southern Hemisphere tropical South America. We show that the most significant vegetation changes occurred in southwest Amazonia and southeast Brazil, regions reliant on precipitation derived from the South American summer monsoon (SASM). A drier mid-Holocene in these regions, linked to a weaker SASM, favored more open vegetation (savannah/grasslands) than present, while increased late-Holocene precipitation drove expansion of humid forests (e.g., evergreen tropical forest in southwest Amazonia, Araucaria forests in southeast Brazil). The tropical forests of central, western and eastern Amazonia remained largely intact throughout this 6000-year period. Northeastern Brazil’s climate is “antiphased” with the rest of tropical South America, but a lack of paleo-data limits our understanding of how vegetation responded to a wetter (drier) mid-(late) Holocene. From this paleo-data perspective, we conclude that ecotonal forests already close to their climatic thresholds are most vulnerable to predicted future drought, but the forest biome in the core of Amazonia is likely to be more resilient. Of greater concern are widespread deforestation and uncontrolled anthropogenic burning, which will decrease ecosystem resilience, making them more vulnerable than they might be without current anthropogenic pressures.