Using a whole-watershed approach and a combination of historical, contemporary, modeled and paleolimnological datasets, we show that the High Arctic's largest lake by volume (Lake Hazen) has succumbed to climate warming with only a ~1 °C relative increase in summer air temperatures. This warming deepened the soil active layer and triggered large mass losses from the watershed's glaciers, resulting in a ~10 times increase in delivery of glacial meltwaters, sediment, organic carbon and legacy contaminants to Lake Hazen, a >70% decrease in lake water residence time, and near certainty of summer ice-free conditions. Concomitantly, the community assemblage of diatom primary producers in the lake shifted dramatically with declining ice cover, from shoreline benthic to open-water planktonic species, and the physiological condition of the only fish species in the lake, Arctic Char, declined significantly. Collectively, these changes place Lake Hazen in a biogeochemical, limnological and ecological regime unprecedented within the past ~300 years.