The late Quaternary period saw the rapid extinction of the majority of the world's terrestrial megafauna. The cause of these dramatic losses, especially the relative importance of climatic change and the impacts of newly arrived people, remains highly controversial, with geographically restricted analyses generating conflicting conclusions. By analyzing the distribution and timing of all megafaunal extinctions in relation to climatic variables and human arrival on five landmasses, we demonstrate that the observed pattern of extinctions is best explained by models that combine both human arrival and climatic variables. Our conclusions are robust to uncertainties in climate data and in the dates of megafaunal extinctions and human arrival on different landmasses, and strongly suggest that these extinctions were driven by both anthropogenic and climatic factors.