Despite being a finite resource, both the quality and quantity of groundwater are under tremendous pressure due to rapid global changes, viz. population growth, land-use/land-cover changes (LULC), and climate change. The 6th Sustainable Development Goal (SDG) aims to “Ensure availability and sustainable management of water and sanitation for all”. One of the most significant dimensions of the SDG agenda is the emphasis on data and governance. However, the lack of good governance coupled with good observed data cannot ensure the achievement of SDG6. Therefore, this study strives to evaluate water quality status and hydrochemical processes governing it in the data-scarce Mokopane area of South Africa. Groundwater is the main source of fresh water supply for domestic usage, intensive agriculture, and mining activities in Mokopane. In this study, hydrogeochemical analysis of groundwater samples was employed to calculate the water quality index (WQI) and evaluate factors governing water quality evolution in the study area. Statistical and spatial analysis techniques were carried out to divide sampling sites into clusters and delineate principal factors responsible for determining water quality of the sampled groundwater. Results suggest that most of the physico-chemical parameters are within permissible limits for drinking water set by the World Health Organization (WHO), except for high fluoride in some samples. Na-HCO3 is the most abundant water type followed by Mg-HCO3, which indicates dominance of Na+, Mg2+, and HCO3±. Rock-water interaction is the prime factor responsible for fluoride enrichment in water. The alkaline nature of groundwater favors the release of exchangeable F− from minerals like muscovite. The WQI suggests that 80% of water samples fall into the good and excellent categories. Poor management of untreated domestic sewage and agricultural runoff is a main factor for the bad/very bad categories of water samples. As the area lacks any credible scientific/government work to report water quality and its management aspects, the findings of this study will definitely help both scientific communities and policy makers to do what is needed for sustainable water resource management in a timely manner.