The objective of this study was to quantify the coverage of Kariba weed (Salvinia molesta) on lakes Kyoga and Kwania and document the environmental and socio-economic impacts associated with its infestation. Data on weed infestation status was collected in 2017 and compared with pre-infestation period of 2013. Weed infestations were approximately 15,643 and 13,688 ha on lakes Kyoga and Kwania respectively. The infestation impaired fishing activities, water quality, water abstraction and water transport. They also led to 20.4, 60.1, 7.7, 17.6 and 5.7 kg reduction in catches per day for Tilapia, Mukene, Catfish, Nile perch and Mudfish respectively. The infestations were also associated with a general increase in the prices of the fish. Individual fishermen registered losses in fish revenue. Household spent approximately UGX 108,523 annually as treatment costs for diseases associated with weed infestation. While 32% of the respondents tried to manually control the waterweed at approximately UGX 83,988/year, the mobile nature of the weed rendered these efforts unsuccessful. A strategy to sustainably control the waterweed using specific bio-control agents (Cyrtobagous salviniae) is recommended.