Lack of fire in contemporary grasslands has contributed to the invasion of woody plants that can survive low-intensity fire upon maturity, but knowledge of the effects of megafires (>40,000 ha) on grassland tree mortality is limited. We used remote sensing and ground surveys to estimate tree canopy cover change and rates of top-kill and mortality of woody species in the mixed-grass prairie following megafire. After megafire, we detected 63% tree canopy cover loss, 17 ± 4% (mean ± SD) of woodland trees were dead, and 56 ± 5% of tree species were top-killed and resprouted. We conclude that further postfire management (e.g., targeted herbicide, mechanical removal) may be required to limit woody encroachment following megafire.