During the Cretaceous period (∼145–65million years ago), there were several periods of global ocean anoxia, each lasting less than onemillion years. These events, known as ocean anoxic events, were marked by significant increases in organic carbon burial1, and are generally attributed to increased primary productivity in surface waters2. The details underpinning the initiation, maintenance and termination of these events, however, remain equivocal. Here we present sulphur isotope data spanning the Ocean Anoxic Event 2 (about 94.5million years ago) from sedimentary rocks in Colorado that were formed in the Western Interior Seaway; this seaway ran north–south, splitting North America during the Cretaceous. Sulphate levels increased rapidly from relatively low background levels at the onset of the event, most likely from the release of sulphur by massive volcanism, and fell during the anoxic event. We infer that the input of sulphate facilitated increased carbon remineralization, which enhanced nutrient recycling and increased global primary productivity, eventually resulting in widespread ocean anoxia. Our scenario indicates that Ocean Anoxic Event 2 may have persisted until sulphate levels were stabilized by the formation and burial of the sulphur mineral pyrite, which returned primary productivity to background levels. We suggest that fluctuations in sulphate levels may have regulated the marine carbon cycle during past periods of low oceanic sulphate concentration.