Many arid and semi-arid regions of Southern Africa experience pressure on water resources as a result of limited rainfall, droughts, high population growth, and poor infrastructure. To satisfy domestic, agricultural, and livestock demands, multiple water sources are used, but the scientific and local knowledge on both the quality and quantity of these is limited for the study area. As part of SASSCAL Tasks 007, 010 and 014, numerous field campaigns (2013–2017) were carried out in the transboundary Cuvelai-Etosha Basin (CEB) with the aim of providing a comprehensive description of surface and groundwater resources. The investigations reveal that sound management and coordinated use of water resources in the CEB need to be introduced. This could include, for example, adding further responsibilities to water point committees and developing management strategies based on a thorough understanding of hydrologically relevant processes. Sufficient water exists, but its quality and quantity are highly variable. Simple actions at a local scale (e.g., rainwater harvesting, fencing off wells, use of perched aquifers) could improve the situation substantially.