Multistressor global change, the combined influence of ocean warming, acidification, and deoxygenation, poses a serious threat to marine organisms. Experimental studies imply that organisms with higher levels of activity should be more resilient, but testing this prediction and understanding organism vulnerability at a global scale, over evolutionary timescales, and in natural ecosystems remain challenging. The fossil record, which contains multiple extinctions triggered by multistressor global change, is ideally suited for testing hypotheses at broad geographic, taxonomic, and temporal scales. Here, I assess the importance of activity level for survival of well-skeletonized benthic marine invertebrates over a 100-million-year-long interval (Permian to Jurassic periods) containing four global change extinctions, including the end-Permian and end-Triassic mass extinctions. More active organisms, based on a semiquantitative score incorporating feeding and motility, were significantly more likely to survive during three of the four extinction events (Guadalupian, end-Permian, and end-Triassic). In contrast, activity was not an important control on survival during nonextinction intervals. Both the end-Permian and end-Triassic mass extinctions also triggered abrupt shifts to increased dominance by more active organisms. Although mean activity gradually returned toward pre-extinction values, the net result was a permanent ratcheting of ecosystem-wide activity to higher levels. Selectivity patterns during ancient global change extinctions confirm the hypothesis that higher activity, a proxy for respiratory physiology, is a fundamental control on survival, although the roles of specific physiological traits (such as extracellular pCO2 or aerobic scope) cannot be distinguished. Modern marine ecosystems are dominated by more active organisms, in part because of selectivity ratcheting during these ancient extinctions, so on average may be less vulnerable to global change stressors than ancient counterparts. However, ancient extinctions demonstrate that even active organisms can suffer major extinction when the intensity of environmental disruption is intense.