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Paleoenvironmental reconstructions coupled with archaeological research are useful tools for discriminating natural versus anthropogenic environmental variability and identifying local environmental responses to global changes and consequent human adaptations. Here we present a multidisciplinary study focused on the identification of drivers and mechanisms that shaped environments along the Uruguay coast and how those environments influenced prehistoric settlement patterns, subsistence strategies, and site formation processes at the archaeological sites of Cape Polonio and Castillos Lagoon.We identify a strong linkage between environmental dynamics and the timing, spatial allocation, and subsistence strategies of prehistoric inhabitants. Human occupation took place in very specific landscape settings where contemporaneous settlements were identified in persistent eolian landscape features. An opportunistic exploitation of more dynamic locations was also identified, where sea-level shifts created land surfaces preferred by humans. The results of our study represent a useful tool not only for identifying archaeological sites in similar contexts but also for providing insights into how modern coastal populations might adapt to changing environments associated with rising sea level. [ABSTRACT FROM AUTHOR]