Recent climatic change and other factors are causing severe population declines in Yellowstone amphibian populations. We documented severe, significant population extirpations of all four native amphibians, blotched tiger salamander (Ambystoma tigrinum melanostictum), boreal chorus frog (Pseudacris triseriata maculata), Colombia spotted frog (Rana luteiventris) and boreal toad (Bufo boreas boreas). Multiple decades of climatic data showed significant changes in climatic conditions, with decreasing year-round precipitation and increasing temperature during the hottest seasons. Surveys of 49 current and historic bodies of water indicate that these desiccating conditions and increasing temperatures are causing former wetlands to disappear. Over the past 15 years, more than half the pond environments in northern Yellowstone have vanished, and remote sensing analyses further indicate that wetland prevalence is severely declining. Entire amphibian populations have been eradicated from locations that no longer sustain water, and have disappeared even from wetlands that remain hydrated. Even in these hydrated potential habitats, our surveys show that amphibian diversity is at a critical low. Our results indicate that climate change has already disrupted ecosystems in the most protected reserves of our planet, and that current predictions of species vulnerability may not reflect potential impacts of global warming.