Demand for lithium is expected to increase by as much as 40 times over the coming decades. More than half the world’s lithium resources are found in brine aquifers at the intersection of Chile, Argentina, and Bolivia. As lithium exploration increases, accurate estimates of water availability are critical for water management decisions, particularly in this region home to communities and ecosystems relying on limited water resources. We develop the first region-specific water availability assessment with 28 active, near-production, and prospective lithium-producing basins. We modify the AWARE method by re-calculating availability minus demand using a novel available water approach and evaluate the impacts of freshwater use from future lithium mining. Our results reveal that commonly used hydrologic models overestimate streamflow by as much as 6000%, leading to inaccurate water scarcity classifications. We also find that, on average, water availability could decrease by 8-107% depending on lithium production quantity and processing technology.