The deteriorating water quality and increasing pollution of Lake Victoria, Africa’s most important and world’s second-largest freshwater lake, is threatening the critical resource within East Africa, which has profound ecological and socio-economic significance. This comprehensive review investigates the environmental dynamics of the lake, exploring temporal trends in water quality, heavy metals, microplastics, and emerging organic pollutants in Kenyan, Tanzanian, and Ugandan waters. Assessing the period from January 2000 to December 2022, the analysis integrates research findings from Lake Victoria and its basin. A complex interaction between natural processes and human activity causes fluctuations in the water quality of Lake Victoria. The study reveals substantial variations in key parameters, reflecting the impacts of industrial discharges, agricultural practices, urbanization, and wastewater inputs. Noteworthy among these variations are heavy metal concentrations, with lead consistently surpassing the acceptable levels in Kenyan and Ugandan waters. Zinc concentrations showed varying patterns, and chromium levels in sediments raise concerns by surpassing EPA guidelines in specific locations. The investigation of organic pollutants identified over 170 contaminants, highlighting the dominance of dichlorodiphenyltrichloroethane (DDT) and its derivatives. Microplastics, recognized in the guts of vital fish species and surface water, merge as a growing concern, posing risks to the aquatic ecosystem. This review illuminates the nature of pollutants in Lake Victoria and identifies knowledge gaps in research attention, especially in the northwestern, western, and southwestern lake basins, and the islands of Lake Victoria, overlooked for more than two decades. Scrutinizing existing research, it serves as a compass, pointing towards areas necessitating further investigation and thereby charting future directions in the research community.