Building on previous analyses suggesting that the composition of fishery landings reflects the effects of eutrophication on mobile fish and benthos, we examined landings composition in relation to nitrogen loading and the spatial extent of hypoxia in a cross-system comparison of 22 ecosystems. We hypothesized that explicit consideration of both N and hypoxia is important because nutrient enrichment has been shown to have contrasting direct and indirect effects on fisheries. Consistent with this premise, patterns in landings composition differed with respect to N load and the spatial extent of hypoxia. For example, the ratios of pelagic to benthic and demersal biomass in fishery landings (P/D) exhibited a decreasing trend across ecosystems with progressively higher N but were significantly and positively correlated with the spatial extent of hypoxia. The P/D ratios were particularly high in systems with extensive and persistent hypoxia and particularly low in several estuaries where purse seining is prohibited or not used. In analyses that considered all systems, benthic and demersal landings did not decrease at high N as predicted by previous conceptual models, and the negative association with the spatial extent of hypoxia was statistically significant only when the Black Sea was included in the analysis. Landings of pelagic planktivores did not vary with the spatial extent of hypoxia but were positively related to N for all systems combined and for semi-enclosed seas. The trophic and size composition of fishery landings were not related to N or hypoxia, perhaps because landings of large, high-trophic-level species are more influenced by fishery exploitation or practices that mask the effects of water quality. Our results suggest that the response of fisheries to eutrophication differs from prevailing paradigms, which do not clearly distinguish between nutrient and hypoxia effects on fishery landings and do not consider the important influence of fishing practices and regulations on patterns in landings data.