In post-Cambrian time, life on Earth experienced 5 major extinction events, likely instigated by adverse environmental conditions. Biodiversity loss among marine taxa, for at least 3 of these mass extinction events (Late Devonian, end-Permian and end-Triassic), has been connected with widespread oxygen-depleted and sulfide-bearing marine water. Furthermore, geochemical and sedimentary evidence suggest that these events correlate with rather abrupt climate warming and possibly increased terrestrial weathering. This suggests that biodiversity loss may be triggered by mechanisms intrinsic to the Earth system, notably, the biogeochemical sulfur and carbon cycle. This climate warming feedback produces large-scale eutrophication on the continental shelf, which, in turn, expands oxygen minimum zones by increased respiration, which can turn to a sulfidic state by increased microbial-sulfate reduction due to increased availability of organic matter. A plankton community turnover from a high-diversity eukaryote to high-biomass bacterial dominated food web is the catalyst proposed in this anoxia-extinction scenario and stands in stark contrast to the postulated productivity collapse suggested for the end-Cretaceous mass extinction. This cascade of events is relevant for the future ocean under predicted greenhouse driven climate change. The exacerbation of anoxic “dead” zones is already progressing in modern oceanic environments, and this is likely to increase due to climate induced continental weathering and resulting eutrophication of the oceans.