The Mekong River Delta is the rice production hub in South-east Asia and has a key role in determining rice prices in the world market. The increasing variability in the local climate due to global climate changes and the increasing severity of the ENSO phenomenon threatens rice production in the region, which has consequences for local and global food security. Though existing mapping efforts delineate the consequences of saline water intrusion during El Niño and flooding events during La Niña in the basin, research to predict future impacts in rice production is rather limited. The current work uses ORYZA, an ecophysiological model, combined with historical climate data, climate change scenarios RCP4.5 and 8.5 and climate-related risk maps to project the aggregate productivity and rice production impacts by the year 2050. Results show that in years of average salinity intrusion and flooding, the winter-spring rice crop in the MRD would experience an average annual decrease of 720,450 tons for 2020-2050 under the RCP4.5 scenario compared to the baseline of 2005-2016 average and another 1.17 million tons under the RCP8.5 scenario. The autumn-winter crop would decrease by 331,480 tons under RCP4.5 and 462,720 tons under RCP8.5. In years of severe salinity intrusion and flooding, the winter-spring rice crop would decrease by 2.13 million tons (10.29% lower than the projection for an average year) under RCP4.5 and 2.5 million tons (13.62%) under RCP8.5. Under severe conditions, the autumn-winter crop would have an average decrease of 1.3 million tons (7.36%) under RCP4.5 and 1.4 million tons (10.88%) for the RCP8.5 scenario. Given that most of the rice produced in this area is exported, a decline in rice supply at this scale would likely have implications on the global market price of rice affecting global food security. Such decline will also have implications for the rural economy and food security of Vietnam. Suggestions for corrective measures to reduce the impacts are briefly discussed.