As heatwaves become more frequent, intense, and longer-lasting due to climate change, the question of breaching thermal limits becomes pressing. A wet-bulb temperature (T_w) of 35 °C has been proposed as a theoretical upper limit on human abilities to biologically thermoregulate. But, recent—empirical—research using human subjects found a significantly lower maximum T_w at which thermoregulation is possible even with minimal metabolic activity. Projecting future exposure to this empirical critical environmental limit has not been done. Here, using this more accurate threshold and the latest coupled climate model results, we quantify exposure to dangerous, potentially lethal heat for future climates at various global warming levels. We find that humanity is more vulnerable to moist heat stress than previously proposed because of these lower thermal limits. Still, limiting warming to under 2 °C nearly eliminates exposure and risk of widespread uncompensable moist heatwaves as a sharp rise in exposure occurs at 3 °C of warming. Parts of the Middle East and the Indus River Valley experience brief exceedances with only 1.5 °C warming. More widespread, but brief, dangerous heat stress occurs in a +2 °C climate, including in eastern China and sub-Saharan Africa, while the US Midwest emerges as a moist heat stress hotspot in a +3 °C climate. In the future, moist heat extremes will lie outside the bounds of past human experience and beyond current heat mitigation strategies for billions of people. While some physiological adaptation from the thresholds described here is possible, additional behavioral, cultural, and technical adaptation will be required to maintain healthy lifestyles.