This data release includes results of raw water, soil, seston, and fish tissue samples collected from 14 lakes within Lake Clark National Park and Katmai National Park between 2007 and 2017. Specifically, these data include total mercury and methylmercury concentrations in water, size-sieved seston, and particulate matter. Additionally, these data include soil and volcanic ash measurements from the surrounding watersheds. Finally, these data include energetic profiling of seston, lake trout (Salvelinus namaycush), and sockeye salmon (Oncorhynchus nerka) as well as mercury isotope measurements of the fishes. These data, except for Lake Clark data, were use in interpreting mercury mass balance flows and bioavailability to the food web and are a part of an associated journal article published in Environmental Science and Technology Letters (https://doi.org/10.1021/acs.estlett.2c00096). Lake Clark data include mercury and methylmercury concentrations in water, seston, and fish tissue from 2011 and 2012. Mercury isotope measurements were not collected as part of this assessment. These data were used to understand drivers of bioaccumulation within predator fish from southwest Alaska and are part of an associated journal article published in Environmental Pollution (https://doi.org/10.1016/j.envpol.2023.121678).