Coastal hypoxia is a growing problem worldwide, but economic consequences for fisheries are largely unknown. We provide evidence that hypoxia causes economic effects on a major fishery that was once the most valuable fishery in America. Our analysis is also a breakthrough in causal inference for coupled human-natural systems. Although establishing causality with observational data is always challenging, feedbacks across the human and natural systems amplify these challenges and explain why linking hypoxia to fishery losses has been elusive. We offer an alternative approach using a market counterfactual that is immune to contamination from feedbacks in the coupled system. Natural resource prices can thus be a means to assess the significance of an ecological disturbance.