Anomalously high water temperatures, associated with climate change, are increasing the global prevalence of coral bleaching, coral diseases, and coral-mortality events. Coral bleaching and disease outbreaks are often inter-related phenomena, since many coral diseases are a consequence of opportunistic pathogens that further compromise thermally stressed colonies. Yet, most coral diseases have low prevalence (<5%), and are not considered contagious. By contrast, we document the impact of an extremely high-prevalence outbreak (61%) of white-plague disease at 14 sites off southeastern Florida. White-plague disease was observed near Virginia Key, Florida, in September 2014, and after 12 months had spread 100 km north and 30 km south. The disease outbreak directly followed a high temperature coral-bleaching event and affected at least 13 coral species. Eusmilia fastigiata, Meandrina meandrites, and Dichocoenia stokesi were the most heavily impacted coral species, and were reduced to <3% of their initial population densities. A number of other coral species, including Colpophyllia natans, Pseudodiploria strigosa, Diploria labyrinthiformis, and Orbicella annularis were reduced to <25% of their initial densities. The high prevalence of disease, the number of susceptible species, and the high mortality of corals affected suggests this disease outbreak is arguably one of the most lethal ever recorded on a contemporary coral reef.