Hunter-gatherers that spread after the Last Glacial Maximum, developed a wide range of strategies to cope with environments subject to major socio-ecological transformations. The Pampa del Tamarugal (PdT), in the hyperarid core of the Atacama Desert, was tied to episodic regional positive hydroclimate anomalies (Central Andean Pluvial Events, CAPE), which enhanced bioproductivity and marked diversity of resources that transformed the basin into an ecological refuge, well suited for hunting small and medium-sized fauna, gathering plants and firewood, and procuring types of lithic raw materials for tool production. Two distinct settlement systems were developed along Quebrada Mani wetlands and Pampa Ramaditas floodplains in the PdT basin, where excavations have yielded well-dated zooarchaeological and archaeological assemblages. Quebrada Mani (ca. 12.8-11.2 ka) functioned a seasonal residential camp under the protection and fertility of wetland and woodland. There, people captured, processed, and consumed a wide range of small and middle size fauna including rodents, birds, and guanacos. In contrast, at the slightly younger (ca. 12.4-11.3 ka) Pampa Ramaditas open riverine landscapes, people stablished short-term non-residential camps, consuming small game. We conclude that Pampa del Tamarugal played a key role in the early history of human dispersal and settlement in South America.