Hydropower contributed to about 86% of Uganda’s total electricity generation in 2016 (UBOS, 2016). With more than 2000 MW of investments in the pipeline, within the next decade (Platts 2016), this technology is expected to play a critical role in Uganda’s transition to a higher consumption level in the multi-tier framework for measuring energy access (MEMD 2015). Competition for water sources is a common challenge among its users. In this case, hydropower infrastructure is not an exception, and water allocation is frequently prioritized to supply domestic and agriculture sectors.With Uganda’s population expected to double by 2050 compared to 2015 levels (UNDESA 2017), the competition for water among the different sectors is only expected to increase. In addition to this, climatic variables, like precipitation and temperature, introduce a high variability in the availability of surface water (Maslin and Austin 2012). Hence, before locking down on major infrastructure decisions as is the case of large-scale hydropower plants (>100 MW), it is prudent to take into consideration the cross-sectorial dependencies, trade-offs, and potential impacts of climate variability. This study develops a methodology based on the established Climate, Land, Energy and Water strategies (CLEWs) framework (Howells et al. 2013) to assess the vulnerability of the electricity sector to climate change by also considering minimum environmental flows in major Ugandan rivers. This assessment utilizes the cost of electricity generation as an indicative metric to compare conditions of different hydropower output, in light of changing climates and hypothetical environmental flow constraints. It concludes that irrespective of the climate, if key environmental services have to be maintained, there will be a reduction in hydropower generation in the country, and proper adaptation measures need to be taken to avoid disruptions in power supply.