Lake Bosomtwe has been subjected to anthropogenic perturbations that provide different scales of environmental stimuli in response to seasonal variation. This situation can overwhelm the capacity of lake to mitigate the impact on the water quality. Knowledge of seasonality will enhance the predictability of the water quality trends to advance management of the lake. The seasonal pattern of levels of physicochemical and nutrient parameters was examined, from March 2018 to February 2020, using the Canadian Council of Ministers of the Environment Water Quality Index model. Temperature, pH, alkalinity, turbidity, dissolved oxygen, total hardness, total dissolved solids, total suspended solids, biochemical oxygen demand, nitrate, phosphate, sulphate, iron, lead, and zinc were studies. The results showed a decline in water quality from ‘fair’ status in the pre-rainy (65.7%) and rainy (67.2%) seasons through ‘marginal’ in the pre-dry seasons (46.5%) to poor in the dry seasons (44%). The lake is therefore losing its natural protection to the extent of occasional for the pre-rainy and rainy seasons, frequently for pre-dry seasons, and almost all the time for dry season, the period of low lake water volume and availability and hence high dependence. Thus, the threat of human and ecological health hazard associated with aquatic pollution is ordered by seasonality; being heightened in the dry season with alkalinity, sulphate, iron, temperature, total suspended solids and turbidity as the parameters of more concern. This provides adequate ground for a call for elaborate and systematic plan of action to manage the lake for sustainability.