A hydrogeological study of the shallowest part of the halite nucleus of the Salar de Atacama is presented, focusing on the isotopic variability in δ18O and δ2H (SMOW) in the brine. It is observed that intensive brine extraction has induced upward vertical flows from the lower aquifer, which presents with a lighter isotopic composition (δ18O: −0.87‰ to −2.49‰; δ2H: −26.04‰ to −33.25‰), toward the upper aquifer, which has more variable and enriched isotopic values. Among the possible explanations for the lighter isotopic composition of the lower aquifer waters is the influence of paleolakes formed during the wetter periods of the Late Pleistocene and Holocene that recharged the underlying aquifers. The geological structure of the Salar, including faults and the distribution of low-permeability layers, has played a determining role in the system’s hydrodynamics. This study emphasizes the need for continuous and detailed monitoring of the isotopic composition to assess the sustainability of the water resource in response to brine extraction and future climate changes. Additionally, it suggests applying this methodology to other salt flats in the region for a better understanding of hydrogeological processes in arid zones. The research provides an integrative view of the relationship between resource extraction, water management, and ecosystem conservation in one of the most important salars in the world.