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Groundwater-dependent species are among the least-known components of global biodiversity, as well as some of the most vulnerable because of rapid groundwater depletion at regional and global scales. The karstic Edwards-Trinity aquifer system of west-central Texas is one of the most species-rich groundwater systems in the world, represented by dozens of endemic groundwater-obligate species with narrow, naturally fragmented distributions. Here, we examine how geomorphological and hydrogeological processes have driven population divergence and speciation in a radiation of salamanders (Eurycea) endemic to the Edwards-Trinity system using phylogenetic and population genetic analysis of genome-wide DNA sequence data. Results revealed complex patterns of isolation and reconnection driven by surface and subsurface hydrology, resulting in both adaptive and nonadaptive population divergence and speciation. Our results uncover cryptic species diversity and refine the borders of several threatened and endangered species. The US Endangered Species Act has been used to bring state regulation to unrestricted groundwater withdrawals in the Edwards (Balcones Fault Zone) Aquifer, where listed species are found. However, the Trinity and Edwards-Trinity (Plateau) aquifers harbor additional species with similarly small ranges that currently receive no protection from regulatory programs designed to prevent groundwater depletion. Based on regional climate models that predict increased air temperature, together with hydrologic models that project decreased spring-flow, we conclude that Edwards-Trinity salamanders and other codistributed groundwater-dependent organisms are highly vulnerable to extinction within the next century.