Rising temperatures and specific humidity are compounding influences that increase heat stress and reduce safe labor capacity. Here, we evaluate reductions in summertime labor capacity using Large Ensemble experiments from two Earth System Models (ESMs). Vulnerable regions, including the Indian subcontinent, Southeast Asia, and West Africa, are expected to begin experiencing 25% reductions as early as the 2040s. Internal climate variability can cloud the timing of such reductions, with differences in onset between ensemble members exceeding 40 years in high-variability locations. At regional scales, onset times are more certain, with differences between ensemble members typically less than 20 years. We demonstrate the benefits for maintaining human labor capacity associated with limiting the increase in global mean surface temperature (ΔGMST) to 1.5°C, consistent with the Paris Agreement. If ΔGMST exceeds 3.5°C, at least 15% of the global population is projected to experience 50% reductions in summertime labor capacity.