The Lower Mekong River basin (LMB) has experienced droughts in recent decades, causing detrimental economic losses and food security conundrums. This study quantified the impact of climate change on drought, and rainfed rice production in the LMB. The Soil and Water Assessment Tool (SWAT) and AquaCrop models were used to evaluate long-term drought indices and rainfed rice yields under historical and future climate conditions (1954-2099) with four climate models and two emission scenarios (RCP 4.5 and RCP8.5) from the Coupled Model Intercomparison Project Phase 5 (CMIP5). We found that rice yield might increase (24-43%) due to the elevated levels of atmospheric CO2 concentration (+ 34.3 to + 121.9%) and increases in precipitation. Contrastingly, considerable decreases in rice yield up to 1.5 ton/ha in the Vietnam Central High Plain (VCHP) region could be expected resulting from reduced precipitation by about 34% during drought years. To avert any major food crisis, an expansion of irrigation areas could be required to compensate for the expected reduction in rice yields. We conclude that a framework combining hydrology and crop models to assess climate change impacts on food production is key to develop adaptation strategies in the future.