Global temperatures and infectious disease outbreaks are simultaneously increasing, but linking climate change and infectious disease to modern extinctions remains difficult. Thethermal mismatch hypothesispredicts that hosts should be vulnerable to disease at temperatures where the performance gap between themselves and parasites is greatest. This framework could be used to identify species at risk from a combination of climate change and disease because it suggests that extinctions should occur when climatic conditions shift from historical baselines. We conducted laboratory experiments and analyses of recent extinctions in the amphibian genusAtelopusto show that species from the coldest environments experienced the greatest disease susceptibility and extinction risk when temperatures rapidly warmed, confirming predictions of thethermal mismatch hypothesis. Our work provides evidence that a modern mass extinction was likely driven by an interaction between climate change and infectious disease.