We have discovered 2 major oceanic anoxic events (OAEs) in the early Cambrian at the time when animals markedly diversified. We present a multiproxy constraint on the global biogeochemical cycles to show that these events, in contrast to most younger OAEs, could have been driven by declining atmospheric O₂ levels, plausibly set off by the appearance of bioturbating animals. Pulses of animal appearances may have occurred at different times on different continents, but the last pulse occurred after the OAEs and at a time when we predict higher marine productivity and O₂ levels in the surface oceans suggesting energy supply into the marine food chain was maximal.The proliferation of large, motile animals 540 to 520 Ma has been linked to both rising and declining O₂ levels on Earth. To explore this conundrum, we reconstruct the global extent of seafloor oxygenation at approximately submillion-year resolution based on uranium isotope compositions of 187 marine carbonates samples from China, Siberia, and Morocco, and simulate O₂ levels in the atmosphere and surface oceans using a mass balance model constrained by carbon, sulfur, and strontium isotopes in the same sedimentary successions. Our results point to a dynamically viable and highly variable state of atmosphere–ocean oxygenation with 2 massive expansions of seafloor anoxia in the aftermath of a prolonged interval of declining atmospheric pO₂ levels. Although animals began diversifying beforehand, there were relatively few new appearances during these dramatic fluctuations in seafloor oxygenation. When O₂ levels again rose, it occurred in concert with predicted high rates of photosynthetic production, both of which may have fueled more energy to predators and their armored prey in the evolving marine ecosystem.