The water quality of the Upper Okavango River has been described as pristine for many years since the water chemistry of the system was first studied. However, modern developmental activities and natural environmental processes are now threatening the quality and quantity of this river water. Continuous monitoring is important for providing scientific data that can be used to detect early warning signs of system changes and support effective management and protection of the resource. In this project, water quality of the Upper Okavango delta (Panhandle) was studied continuously from July 2014 to 2017 using physicochemical parameters. Field parameters were measured on-site using calibrated meters, and major ions were analysed in the laboratory using standard methods. Levels of electrical conductivity, pH, dissolved oxygen, and turbidity showed significant differences between sampling sites but still within international freshwater and drinking water guidelines. Statistical analysis showed no significant variations in water quality parameters over the years of the study. Parameters displayed seasonal cyclic variations controlled mainly by temperature (concentrated chemical species in summer) and flood levels (diluted most parameters during high floods). High floods also reduced dissolved oxygen concentration in river waters to a minimum of less than 1 mg/l, concentrations lethal to aquatic organisms, especially fish. This depletion occurred because high floodwaters bring in high levels of organic matter, which has a high oxygen demand for decomposition processes. The ionic composition of the Panhandle waters was found to be dominated by calcium (1.1–32.8 mg/l) and bicarbonate (0.9–77.2 mg/l), but still remained fresh. Although major land use changes are reported in the upper Namibian Kavango area, no apparent impact on water quality has been observed in this study.