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Anthropogenic climate warming has increased the likelihood of extreme hot summers. To facilitate mitigation and adaptation planning, it is essential to quantify and synthesize climate change impacts and characterize the associated uncertainties. By synergistically using projections of climate scenarios from an ensemble of regional climate models and a spatially explicit version of an empirical health risk model, here we quantify the mortality risk associated with excessive heat stress for people aged over 65years old across the Middle East and North Africa (MENA). Our results show that mortality risk is expected to intensify by a factor of 8-20 in the last 30years of the twenty-first century with respect to the historical period (1951-2005) if no climate change mitigation planning is undertaken. If global warming is limited to 2 degrees C, the mortality risk is expected to rise by a factor of 3-7 for the same period. Further analyses reveal that much of the increase in mortality risk is due to the increase in frequency of warm days rather than their intensity. Unfortunately, the poorest countries with least contribution to climate change are expected to be most impacted by it, as they will experience higher mortality risks compared to wealthier nations.