Aims: To determine the magnitude of microbial risks from waterborne viruses and bacteria in Bwaise III in Kampala (Uganda), a typical slum in Sub-Saharan Africa. Methods and Results: A quantitative microbial risk assessment (QMRA) was carried out to determine the magnitude of microbial risks from waterborne pathogens through various exposure pathways in Bwaise III in Kampala (Uganda). This was based on the concentration of Escherichia coli O157:H7, Salmonella spp., rotavirus (RV) and human adenoviruses F and G (HAdV) in spring water, tap water, surface water, grey water and contaminated soil samples. The total disease burden was 680 disability-adjusted life years (DALYs) per 1000 persons per year. The highest disease burden contribution was caused by exposure to surface water open drainage channels (39%) followed by exposure to grey water in tertiary drains (24%), storage containers (22%), unprotected springs (8%), contaminated soil (7%) and tap water (0·02%). The highest percentage of the mean estimated infections was caused by E. coli O157:H7 (41%) followed by HAdV (32%), RV (20%) and Salmonella spp. (7%). In addition, the highest infection risk was 1 caused by HAdV in surface water at the slum outlet, while the lowest infection risk was 2·71 × 10^-6 caused by E. coli O157:H7 in tap water. Conclusions: The results show that the slum environment is polluted, and the disease burden from each of the exposure routes in Bwaise III slum, with the exception of tap water, was much higher than the WHO reference level of tolerable risk of 1 × 10^-6 DALYs per person per year. Significance and Impact of the Study: The findings of this study provide guidance to governments, local authorities and nongovernment organizations in making decisions on measures to reduce infection risk and the disease burden by 10² to 10⁵ depending on the source of exposure to achieve the desired health impacts. The infection risk may be reduced by sustainable management of human excreta and grey water, coupled with risk communication during hygiene awareness campaigns at household and community level. The data also provide a basis to make strategic investments to improve sanitary conditions in urban slums.