The Mississippi River watershed drains 40% of the continental United States, and the tremendous primary productivity in the adjacent north-central Gulf of Mexico has created one of the most extensive dead zones on Earth. In contrast, smaller watersheds deliver less nutrients to the northeastern Gulf, and consequently productivity is limited and hypoxia is uncommon. How has variation in primary productivity, oxygen availability, and sea surface temperature, affected coastal food webs? Here, we investigate environmental controls on the size of molluscan predators and prey in the northern Gulf of Mexico using Holocene death assemblages. Linear mixed models indicate that bivalve size and the frequency of drilling predation are affected by dissolved oxygen concentrations; drilling frequency declines with declining oxygen, whereas bivalve size increases. In contrast, sea surface temperature is positively associated with the size of molluscan predators and prey. Net primary productivity contributes relatively little to predator or prey size, and predator-to-prey size ratios do not vary consistently with environmental conditions across the northern Gulf. Larger bivalves in areas of oxygen limitation may be due to decreased predation pressure and consequently greater prey longevity. The larger size of bivalves and predatory gastropods in warmer waters may reflect enhanced growth under these conditions, provided dissolved oxygen concentrations exceed a minimum threshold. Holocene death assemblages can be used to test long-standing hypotheses regarding environmental controls on predator-prey body size distributions through geologic time and provide baselines for assessing the ongoing effects of anthropogenic eutrophication and warming on coastal food webs.