Climate, competition, and disease are well-recognized drivers of population dynamics. These stressors can be intertwined by animal migrations, leading to uncertainty about the roles of natural and anthropogenic factors in conservation and resource management. We quantitatively assessed the four leading hypotheses for an enigmatic long-term decline in productivity of Canada's iconic Fraser River sockeye salmon: (1) delayed density-dependence, (2) local oceanographic conditions, (3) pathogen transmission from farmed salmon, and (4) ocean-basin scale competition with pink salmon. Our findings suggest that the long-term decline is primarily explained by competition with pink salmon, which can be amplified by exposure to farmed salmon early in sockeye marine life, and by a compensatory interaction between coastal ocean temperature and farmed-salmon exposure. These correlative relationships suggest oceanic-scale processes, which are beyond the reach of current regulatory agencies, may exacerbate local ecological processes that challenge the coexistence of fisheries and aquaculture-based economies in coastal seas.