Contamination of drinking water by potentially toxic elements (PTEs) remains a critical public-health concern in Uganda. This systematic review compiled and harmonized quantitative concentrations (mg/L) for key PTEs, lead (Pb), cadmium (Cd), arsenic (As), chromium (Cr), mercury (Hg), copper (Cu), zinc (Zn), nickel (Ni), cobalt (Co), manganese (Mn), and iron (Fe), across various potable and informal water sources used for drinking, including municipal tap water, boreholes, protected and unprotected springs, wells, rainwater, packaged drinking water, rivers, lakes, and wetlands. A comprehensive search of different databases and key institutional repositories yielded 715 records; after screening and eligibility assessment, 161 studies met the inclusion criteria, and were retained for final synthesis. Reported PTE concentrations frequently exceeded WHO and UNBS drinking water guidelines, with Pb up to 8.2 mg/L, Cd up to 1.4 mg/L, As up to 25.2 mg/L, Cr up to 148 mg/L, Fe up to 67.3 mg/L, and Mn up to 3.75 mg/L, particularly in high-risk zones such as Rwakaiha Wetland, Kasese mining affected catchments, and Kampala’s urban springs and drainage corridors. These hotspots are largely influenced by mining activities, industrial discharges, agricultural runoff, and corrosion of aging water distribution infrastructure, while natural geological conditions contribute to elevated background Fe and Mn in several regions. The review highlights associated health implications, including neurological damage, renal impairment, and cancer risks from chronic exposure, and identifies gaps in regulatory enforcement and routine monitoring. It concludes with practical recommendations, including stricter effluent control, expansion of low-cost adsorption and filtration options at household and community level, and targeted upgrades to water-treatment and distribution systems to promote safe-water access and support Uganda’s progress toward Sustainable Development Goal 6.