Methylmercury contamination of fish is a global threat to environmental health. Mercury (Hg) monitoring programs are valuable for generating data that can be compiled for spatially broad syntheses to identify emergent ecosystem properties that influence fish Hg bioaccumulation. Fish total Hg (THg) concentrations were evaluated across the Western United States (US) and Canada, a region defined by extreme gradients in habitat structure and water management. A database was compiled with THg concentrations in 96,310 fish that comprised 206 species from 4262 locations, and used to evaluate the spatial distribution of fish THg across the region and effects of species, foraging guilds, habitats, and ecoregions. Areas of elevated THg exposure were identified by developing a relativized estimate of fish mercury concentrations at a watershed scale that accounted for the variability associated with fish species, fish size, and site effects. THg concentrations in fish muscle ranged between 0.001 and 28.4 (ÎŒg/g wet weight (ww)) with a geometric mean of 0.17. Overall, 30% of individual fish samples and 17% of means by location exceeded the 0.30ÎŒg/g ww US EPA fish tissue criterion. Fish THg concentrations differed among habitat types, with riverine habitats consistently higher than lacustrine habitats. Importantly, fish THg concentrations were not correlated with sediment THg concentrations at a watershed scale, but were weakly correlated with sediment MeHg concentrations, suggesting that factors influencing MeHg production may be more important than inorganic Hg loading for determining fish MeHg exposure. There was large heterogeneity in fish THg concentrations across the landscape; THg concentrations were generally higher in semi-arid and arid regions such as the Great Basin and Desert Southwest, than in temperate forests. Results suggest that fish mercury exposure is widespread throughout Western US and Canada, and that species, habitat type, and region play an important role in influencing ecological risk of mercury in aquatic ecosystems.