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Western North America is a region defined by extreme gradients in geomorphology and climate, which support a diverse array of ecological communities and natural resources. The region also has extreme gradients in mercury (Hg) contamination due to a broad distribution of inorganic Hg sources. These diverse Hg sources and a varied landscape create a unique and complex mosaic of ecological risk from Hg impairment associated with differential methylmercury (MeHg) production and bioaccumulation. Understanding the landscape-scale variation in the magnitude and relative importance of processes associated with Hg transport, methylation, and MeHg bioaccumulation requires a multidisciplinary synthesis that transcends small-scale variability. The Western North America Mercury Synthesis compiled, analyzed, and interpreted spatial and temporal patterns and drivers of Hg and MeHg in air, soil, vegetation, sediments, fish, and wildlife across western North America. This collaboration evaluated the potential risk from Hg to fish, and wildlife health, human exposure, and examined resource management activities that influenced the risk of Hg contamination. This paper integrates the key information presented across the individual papers that comprise the synthesis. The compiled information indicates that Hg contamination is widespread, but heterogeneous, across western North America. The storage and transport of inorganic Hg across landscape gradients are largely regulated by climate and land-cover factors such as plant productivity and precipitation. Importantly, there was a striking lack of concordance between pools and sources of inorganic Hg, and MeHg in aquatic food webs. Additionally, water management had a widespread influence on MeHg bioaccumulation in aquatic ecosystems, whereas mining impacts where relatively localized. These results highlight the decoupling of inorganic Hg sources with MeHg production and bioaccumulation. Together the findings indicate that developing efforts to control MeHg production in the West may be particularly beneficial for reducing food web exposure instead of efforts to simply control inorganic Hg sources. Published by Elsevier B.V.