Global climate projections suggest a significant intensification of summer heat extremes in the Middle East and North Africa (MENA). To assess regional impacts, and underpin mitigation and adaptation measures, robust information is required from climate downscaling studies, which has been lacking for the region. Here, we project future hot spells by using the Heat Wave Magnitude Index and a comprehensive ensemble of regional climate projections for MENA. Our results, for a business-as-usual pathway, indicate that in the second half of this century unprecedented super- and ultra-extreme heatwave conditions will emerge. These events involve excessively high temperatures (up to 56 °C and higher) and will be of extended duration (several weeks), being potentially life-threatening for humans. By the end of the century, about half of the MENA population (approximately 600 million) could be exposed to annually recurring super- and ultra-extreme heatwaves. It is expected that the vast majority of the exposed population (>90%) will live in urban centers, who would need to cope with these societally disruptive weather conditions.