Current greenhouse gas mitigation ambition is consistent with ~3 degrees C global mean warming above preindustrial levels. There is a clear need to strengthen mitigation ambition to stabilize the climate at the Paris Agreement goal of warming of less than 2 degrees C. We specify the differences in city-level heat-related mortality between the 3 degrees C trajectory and warming of 2 degrees and 1.5 degrees C. Focusing on 15 U.S. cities where reliable climate and health data are available, we show that ratcheting up mitigation ambition to achieve the 2 degrees C threshold could avoid between 70 and 1980 annual heat-related deaths per city during extreme events (30-year return period). Achieving the 1.5 degrees C threshold could avoid between 110 and 2720 annual heat-related deaths. Population changes and adaptation investments would alter these numbers. Our results provide compelling evidence for the heat-related health benefits of limiting global warming to 1.5 degrees C in the United States.