The earliest known population of the Atacama Desert coincided with the Central Andean Pluvial Event II (CAPE II), an extensive pluvial event recorded during the Late Pleistocene-Early Holocene (13,800-8,500 cal years BP). A large number of archaeological sites from this period have been found along the borders of the Imilac and Punta Negra (24.5°S) high-altitude basins (ca. 3,000 masl). By combining the results of proxy data obtained from geomorphological, sedimentological, and paleoecological (rodent middens) archives and the spatial location of archaeological sites and radiocarbon series analyses, this paper examines the links between human activities and paleoenvironmental dynamics at different times during CAPE II in the southern Atacama Desert. This is done at a finer spatial and temporal scale than previous studies. The first archaeological sites (ca.12,000-11,200 cal years BP) are concomitant with increased paleowetland occurrence frequency. An occupational hiatus is recorded between 11,200 and 10,800 cal years BP, synchronous with a drop in precipitation and wetland development. This is followed by a displacement of the archaeological sites toward the south-east of the Punta Negra Basin and concomitant again with a second peak of wetland development in the area (10,800-10,400 cal years BP) before the final abandonment of the salt flat margins.