What are the biggest consequences of climate change for marine ecosystems? Is it deoxygenation, thermal stress, ocean acidification, or any combination thereof? The Permian-Triassic climate crisis was an episode of severe and rapid climate warming with similarities to the worst-case projected scenarios for the near future. To better understand which consequences of this climate event led to one of the most severe biodiversity crisis ever, we implemented a novel approach of statistically integrating high-resolution fossil data with high-resolution geochemical data. Our results demonstrate that for equatorial, marine ecosystems, oxygen isotope (temperature proxy) and cadmium isotope (primary productivity proxy) dynamics best explain the marine extinction. This suggests that the biggest threats to past and modern biodiversity in these settings are the impacts of thermal and nutrient stress, as well as associated trophic knock-on effects.