Global change has altered the nature of disturbance regimes, and megafire events are increasingly common. Megafires result in immediate changes to habitat available to terrestrial wildlife over broad landscapes, yet we know surprisingly little about how such changes shape space use of sensitive species in habitat that remains. Functional responses provide a framework for understanding and predicting changes in space use following habitat alteration, but no previous studies have assessed functional responses as a consequence of megafire. We studied space use and tested for functional responses in habitat use by breeding greater sage-grouse (Centrocercus urophasianus) before and after landscape-level changes induced by a >40,000 ha, high-intensity megafire that burned sagebrush steppe in eastern Idaho, USA. We also incorporated functional responses into predictive resource selection functions (RSFs) to map breeding habitat before and after the fire. Megafire had strong effects on the distribution of available resources and resulted in context-dependent habitat use that was heterogeneous across different components of habitat. We observed functional responses in the use and selection of a variety of resources (shrubs and herbaceous vegetation) for both nesting and brood rearing. Functional responses in the use of nesting habitat were influenced by the overarching effect of megafire on vegetation, whereas responses during brood rearing appeared to be driven by individual variation in available resources that were conditional on nest locations. Importantly, RSFs built using data collected prior to the burn also had poor transferability for predicting space use in a post-megafire landscape. These results have strong implications for understanding and predicting how animals respond to a rapidly changing environment, given that increased severity, frequency, and extent of wildfire are consequences of global change with the capacity to reshape ecosystems. We therefore demonstrate a conceptual framework to better understand space use and aid habitat conservation for wildlife in a rapidly changing world.