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An important new hypothesis in landscape ecology is that extreme, decade-scale megadroughts can be potent drivers of rapid, macroscale ecosystem degradation and collapse. If true, an increase in such events under climate change could have devastating consequences for global biodiversity. However, because few megadroughts have occurred in the modern ecological era, the taxonomic breadth, trophic depth, and geographic pattern of these impacts remain unknown. Here we use ecohistorical techniques to quantify the impact of a record, pancontinental megadrought period (1891 to 1903 CE) on the Australian biota. We show that during this event mortality and severe stress was recorded in >45 bird, mammal, fish, reptile, and plant families in arid, semi-arid, dry temperate, and Mediterranean ecosystems over at least 2.8 million km(2) (36%) of the Australian continent. Trophic analysis reveals a bottom-up pattern of mortality concentrated in primary producer, herbivore, and omnivore guilds. Spatial and temporal reconstruction of premortality rainfall shows that mass mortality and synchronous ecosystem-wide collapse emerged in multiple geographic hotspots after 2 to 4 y of severe (>40%) and intensifying rainfall deficits. However, the presence of hyperabundant herbivores significantly increased the sensitivity of ecosystems to overgrazing-induced meltdown and permanent ecosystem change. The unprecedented taxonomic breadth and spatial scale of these impacts demonstrate that continental-scale megadroughts pose a major future threat to global biodiversity, especially in ecosystems affected by intensive agricultural use, trophic simplification, and invasive species.