In a classic analysis of the Phanerozoic fossil record, Sepkoski (1980) determined that all the metazoan classes can be categorized into three great evolutionary faunas: 1) the shelly and trilobite-dominated Cambrian fauna, 2) the brachiopod-dominated Paleozoic fauna, and 3) the mollusk-dominated Modern fauna. The increased diversity associated with the expansion of each new fauna coincides with an exponential decrease in diversity of the preceding fauna, and major questions remain regarding the cause of these faunal turnovers. Here, we use respirometry experiments to investigate whether temperature-dependent hypoxia tolerance differs between extant representatives of the Paleozoic and Modern faunas. Specifically, we can determine the absolute pO₂ tolerance (Pcrit) and the temperature sensitivity of Pcrit of each species by performing respirometry experiments at five different temperature controls spanning 5-28°C. These data suggest that extant representatives of the Paleozoic fauna may have a greater tolerance for hypoxia but are also more vulnerable to changes in temperature than extant representatives of the Modern. We then tested these results using an independent biogeographic dataset that was derived from mapping the oxygen-temperature state space of species’ range data as described in the field guide “Beneath Pacific Tides.” We found similar patterns of temperature-dependent hypoxia tolerance as with the direct respirometry experiments. These physiological differences are hypothesized to relate to underlying respiratory anatomy: compared to the Paleozoic fauna, robust circulatory systems in the Modern fauna help increase water flow past respiratory structures and ameliorate the effects of warming, but come at a higher metabolic cost, resulting in higher Pcrit. Ultimately, these data can help us understand how members of the Modern and Paleozoic fauna may respond to ocean warming and deoxygenation and the physiological mechanism driving the turnover events between evolutionary faunas through the Phanerozoic.