This research integrates data procedures for the delineation of regional ground water flow systems in arid karstic basins with sparse hydrogeologic data using surface topography data, geologic mapping, permeability data, chloride concentrations of ground water and precipitation, and measured discharge data. This integrative data analysis framework can be applied to evaluate arid karstic aquifer systems globally. The accurate delineation of ground water recharge areas in developing aquifer systems with sparse hydrogeologic data is essential for their effective long-term development and management. We illustrate the use of this approach in the Cuatrociénegas Basin (CCB) of Mexico. Aquifers are characterized using geographic information systems for ground water catchment delineation, an analytical model for interbasin flow evaluation, a chloride balance approach for recharge estimation, and a water budget for mapping contributing catchments over a large region. The test study area includes the CCB of Coahuila, Mexico, a UNESCO World Biosphere Reserve containing more than 500 springs that support ground water–dependent ecosystems with more than 70 endemic organisms and irrigated agriculture. We define recharge areas that contribute local and regional ground water discharge to springs and the regional flow system. Results show that the regional aquifer system follows a topographic gradient that during past pluvial periods may have linked the Río Nazas and the Río Aguanaval of the Sierra Madre Occidental to the Río Grande via the CCB and other large, currently dry, upgradient lakes.