In 2015, more than 200,000 saiga antelopes died in 3 weeks in central Kazakhstan. The proximate cause of death is confirmed as hemorrhagic septicemia caused by the bacterium Pasteurella multocida type B, based on multiple strands of evidence. Statistical modeling suggests that there was unusually high relative humidity and temperature in the days leading up to the mortality event; temperature and humidity anomalies were also observed in two previous similar events in the same region. The modeled influence of environmental covariates is consistent with known drivers of hemorrhagic septicemia. Given the saiga population’s vulnerability to mass mortality and the likely exacerbation of climate-related and environmental stressors in the future, management of risks to population viability such as poaching and viral livestock disease is urgently needed, as well as robust ongoing veterinary surveillance. A multidisciplinary approach is needed to research mass mortality events under rapid environmental change.