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Recent exploration has revealed that deep-seated and large groundwater reservoirs in Africa's intracontinental basins can be regarded as an additional strategic resource for supply of drinking water. The origin, genesis and recharge of these groundwater reservoirs, however, are still poorly understood. A multidisciplinary approach involving remote sensing, geophysical surveys and hydraulic investigations, as well as hydrochemical and isotope studies, was pursued to gain better insight into the genesis and the potential of a recently discovered lower Kalahari aquifer (LKA) located in the Zambezi Region (Namibia). The study shows that regional tectonic activity associated with the propagation of the Okavango Rift Zone had a tremendous impact on the drainage evolution and hydrogeological setting of the region. Furthermore, there is geomorphological evidence that the LKAprior to tectonic subsidence and burialwas part of a paleochannel of the upper Zambezi River. Hydraulic continuity could be confirmed by geochemical evolution down the flow path. Cation exchange combined with dissolution of calcite progressively produces alkalinity and sodium and consumes calcium in the north-south direction. Comparison of stable isotope content of the LKA with modern rainfall indicates that the recharge occurred under cooler climate conditions. Analysis of C-14 concentrations and Cl-36/Cl ratios show that the age of the groundwater exceeds 100ka and is hence older than presumed. It is concluded that the assessment of the sedimentology, tectonic structures and geochemistry are key factors for understanding both the paleoclimatic and modern recharge processes of deep-seated aquifer systems.