Agriculture is the backbone of Uganda's economy, with about 24.9% contribution to the gross domestic product (GDP) as per the Uganda National Household Survey 2016/17. Agricultural productivity (yield per hectare) is still low due to the high dependence on rain-fed subsistence farming. Climate change is expected to further reduce the yield per hectare. Therefore, this study aims to evaluate the potential impact of climate change on maize yield in the Victoria Nile Sub-basin using the AquaCrop model. It further assesses the possible adaptation measures to climate change. The Hadley Centre Global Environmental Model version 2-Earth System (HadGEM2-ES) data downloaded from the Coordinated Regional Downscaling Experiment (CORDEX) was used to simulate maize yield in the near future (2021-2040), mid future (2041-2070) and late future (2071-2099). Results show that maize yield is likely to reduce by as high as 1-10%, 2-42% and 1-39% in the near, mid and late futures, respectively, depending on the agro-ecological zone. This decline in maize yield can have a significant impact on regional food security as well as socio-economic well-being since maize is a staple crop. The study also shows that improving soil fertility has no significant impact on maize yield under climate change. However, a combined application of supplementary irrigation and shifting the planting dates is a promising strategy to maintain food security and socio-economic development. This study presents important findings and adaptation strategies that policymakers and other stakeholders such as farmers can implement to abate the effects of climate change on crop production.