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Understanding how human societies interacted with environmental changes is a major goal of archaeology and other socio-natural sciences. In this paper, we assess the human-environment interactions in the Pampa del Tamarugal (PDT) basin of the Atacama Desert over the last 13,000 years. By relying on a socio-environmental model that integrates ecosystem services with adaptive strategies, we review past climate changes, shifting environmental conditions, and the continuities and discontinuities in the nature and intensity of the human occupation of the PDT. As a result we highlight the importance of certain key resources such as water, an essential factor in the long-term trajectory of eco-historical change. Without water the outcome of human societies becomes hazardous.