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Groundwater-dependent, spring-fed ecosystems of the Cuatroci,negas Basin, Coahuila, Mexico, host > 70 endemic species. These desert springs occur primarily aligned along the base of an anticline that bisects the Cuatroci,negas Basin, but the hydrogeologic controls of the springs are poorly understood. The hypothesis that spring locations are controlled by subsurface geology, such as buried anticlines or faulting, versus stratigraphic controls is tested by evaluating: (1) regional structural styles; (2) fracture models of analogous structures; (3) hydrogeologic data; and (4) geophysical surveys. Jurassic and Cretaceous siliciclastic and carbonate rocks deposited on the Coahuila Block west of the Cuatroci,negas Basin have dips < 10A degrees and lack faults because of a structurally rigid granodiorite basement. To the east of the Coahuila Block and around the Cuatroci,negas Basin, the Coahuila Folded Belt has anticlines associated with basement-involved faults, 10-25A degrees backlimb dips, and forelimb dips up to vertical or slightly overturned. Springs in the western sub-basin that represent 85% of total basin discharge are located on zones of highest anticipated fracture density predicted by fracture models of analogous anticlines. Spring waters reveal elevated temperature (32-35A degrees C) and low tritium (< 1 tritium unit). Gravimetry and time-domain electromagnetic surveys correspond with a best-fit Cuatroci,negas Basin hydrogeologic model of fractures associated with reverse faulting controlling spring locations in the western Cuatroci,negas Basin. Springs in the eastern sub-basin are located where ephemeral streams have eroded through confining beds along the base of alluvial fans and lack faulting. Regional variations in structural style are an important control on the location of springs in the Cuatroci,negas Basin.