Namibia is one of the driest countries in southern Africa. Groundwater has played an important role in the development of Namibia. However, like those at some other places in Namibia, groundwater is unsuitable for drinking in parts of the Northwest of Namibia because of its poor quality. It is significant to assess groundwater quality and understand the hydrogeochemical processes for the management and utilization of groundwater resource in this water-short region. In this paper, we report the investigation and assessment of groundwater quality and associated hydrogeochemical processes in the Cuvelai-Etosha Basin and Kaokoveld region, northwestern Namibia. A total of 24 samples were collected for chemistry and stable hydrogen and oxygen isotopes analysis. The groundwater quality was evaluated by single factor index method. Hydrochemical and isotopic (δD and δ¹⁸O) data were used to study the hydrogeochemical processes of groundwater in the areas. The results show that most of the groundwater that originated from precipitation was unacceptable in appearance and tastes, but may be safe for human consumption. The salinity and concentrations of As, U and F⁻ in some of groundwater samples exceeded of the WHO standards. The salinity increase of the groundwater is primarily due to minerals dissolution rather than evaporation. A number of the samples located in the Cuvelai-Etosha Basin and Kaokoveld region are low in TDS. The salinity of them mainly derives from the dissolution of carbonate. Some of the samples located in the west of the Cuvelai-Etosha Basin and Kaokoveld region have medium TDS. The salinity of them originates mainly from the dissolution of carbonate and the oxidation of pyrite. The highest Fe concentration in these samples is up to 13 mg/L. The samples located to the east of Etosha Pan have high TDS. Halite and carbonate dissolution with strong cation exchange are the major source of the high salinity. The low Ca2 + concentrations in groundwater and rich fluorine sediments in Cuvelai-Etosha Basin favor the formation of high F⁻ groundwater. The weak alkaline environment and high HCO3⁻ contents are significant to the higher As and U contents. Insight from this study may be helpful to enhance the understanding of distributions and transfers of major ions and trace elements in groundwater and to improve the management and utilization of groundwater resources in the region and other similar areas. Keywords: Groundwater quality, Salinization, Hydrogeochemical processes, Multivariate statistics, Water-rock interaction, Northwest Namibia.