A collection of 514 stable isotope water samples from the Atacama Desert is being reassessed geostatistically. The evaluation reveals that adjacent Andean catchments can exhibit distinct δ18O and δ2H value ranges in meteoric waters, despite similar sample altitudes of up to 4000 m above sea level (a.s.l.). It is proposed that the individual topographic features of each catchment at the western Andean Precordillera either inhibit or facilitate vapor mixing processes of easterly and westerly air masses with different isotopic compositions. This process likely causes catchment-specific isotope value ranges in precipitations (between −7‰ and −19‰ δ18O) that are being consistently reflected in the isotope values of groundwater and surface waters of these catchments. Further, due to evaporation-driven isotopic fractionation and subsurface water mixing, isotope samples of the regional Pampa del Tamarugal Aquifer plot collectively parallel to the local meteoric water line. Besides, there is no evidence for hydrothermal isotopic water-rock interactions. Overall, the observed catchment-dependent isotope characteristics allow for using δ18O and δ2H as tracers to delineate regionally distinct groundwater compartments and associated recharge areas. In this context, δ18O, δ2H and 3H data of shallow groundwater at three alluvial fans challenge the established idea of recharge from alluvial fans after flash floods.