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Madagascar and the Mascarene Islands of Mauritius and Rodrigues underwent catastrophic ecological and landscape transformations, which virtually eliminated their entire endemic vertebrate megafauna during the past millennium. These ecosystem changes have been alternately attributed to either human activities, climate change, or both, but parsing their relative importance, particularly in the case of Madagascar, has proven difficult. Here, we present a multimillennial (approximately the past 8000 years) reconstruction of the southwest Indian Ocean hydroclimate variability using speleothems from the island of Rodrigues, located ∼1600 km east of Madagascar. The record shows a recurring pattern of hydroclimate variability characterized by submillennial-scale drying trends, which were punctuated by decadal-to-multidecadal megadroughts, including during the late Holocene. Our data imply that the megafauna of the Mascarenes and Madagascar were resilient, enduring repeated past episodes of severe climate stress, but collapsed when a major increase in human activity occurred in the context of a prominent drying trend.