National parks, protected areas considered to be relatively pristine and removed from environmental contaminants, contained levels of mercury in some fish that exceeded thresholds for potential impacts to fish, birds, and humans. We measured mercury (Hg) in more than 1,400 fish from 86 remote lakes and rivers – spanning 16 fish species and 21 national parks in 10 western states – and compared Hg concentrations in the fish to an array of health benchmarks. Across all parks, sites, and species, fish Hg concentrations ranged from 9.9 to 1,109 ng/g ww with a mean of 77.7 ng/g ww. Fish Hg levels varied greatly both among and within parks, suggesting that patterns of Hg risk are driven by processes occurring at site specific, local, and global scales. In most parks, Hg concentrations in fish were moderate to low in comparison with similar fish species from other locations in the western U.S. Mercury concentrations were below EPA’s fish tissue criterion for safe human consumption in 96 percent of the sport fish sampled. However, the average concentration of Hg in sport fish from two sites in Wrangell-St. Elias and Lake Clark (AK) national parks exceeded EPA’s human health criterion. Mercury levels in individual sport fish at some sites from Lassen Volcanic (CA), Mount Rainer (WA), Rocky Mountain (CO), Yellowstone (WY), and Yosemite (CA) national parks also exceeded the human health criterion. Mercury concentrations exceeded the most conservative fish toxicity benchmark at 15% of all sites, and the most sensitive health benchmark for fish-eating birds at 52% of all sites. Exposure to high levels of Hg in humans may cause damage to the brain, kidneys, and the developing fetus. In wildlife, elevated Hg levels can result in reduced foraging efficiency, survival, and reproductive success. Much of the mercury found in these mainly high elevation areas is likely the result of air pollution from outside the parks. Future targeted research and monitoring across park habitats would help identify patterns of Hg distribution across the landscape and facilitate informed management decisions aimed at reducing the ecological risk posed by Hg contamination in sensitive ecosystems protected by the National Park Service.