(en) Recurrent events of severe ocean deoxygenation during the Devonian Period represent major disruptions of the marine environment, yet many mysteries still surround them. To address specific aspects of these events, we use the Earth system model of intermediate complexity cGENIE to investigate the controls on ocean oxygenation through a series of targeted numerical experiments. Our results highlight the dominant role of continental configuration in shaping ocean circulation and modulating the response of oxygenation to other environmental and climatic forcings. We further show that astronomical forcing can strongly influence ocean oxygenation through its control on continental nutrient weathering fluxes and biological productivity, producing substantial spatially contrasted responses, and intervals of eccentricity maxima associated with increased anoxia. Finally, model–data comparisons for the Kellwasser events indicate that increased nutrient availability can adequately reproduce the extent and seafloor fraction of anoxia, providing quantitative benchmarks against which different mechanisms and hypotheses can be tested.