Fire shapes biome distribution and community composition worldwide, and is extensively used as a management tool in flammable landscapes. There is growing concern, however, that fire could increase the vulnerability of native fauna to invasive predators. We developed a conceptual model of the ways in which fire could influence predator–prey dynamics. Using a before–after, control–impact experiment, we then investigated the short-term effects of a prescribed fire on 2 globally significant invasive mesopredators (red fox, Vulpes vulpes, and feral cat, Felis catus) and their native mammalian prey in a fire-prone forest of southeastern Australia. We deployed motion-sensing cameras to assess species occurrence, collected predator scats to quantify diet and prey choice, and measured vegetation cover before and after fire. We examined the effects of the fire at the scale of the burn block (1,190 ha), and compared burned forest to unburned refuges. Pre-fire, invasive predators and large native herbivores were more likely to occur at sites with an open understory, whereas the occurrence of most small- and medium-sized native mammals was positively associated with understory cover. Fire reduced understory cover by more than 80%, and resulted in a 5-fold increase in the occurrence of invasive predators. Concurrently, relative consumption of medium-sized native mammals by foxes doubled, and selection of long-nosed bandicoots (Perameles nasuta) and short-beaked echidnas (Tachyglossus aculeatus) by foxes increased. Occurrence of bush rats (Rattus fuscipes) declined. It was unclear if fire also affected the occurrence of bandicoots or echidnas, as changes coincided with normal seasonal variations. Overall, prescribed fire promoted invasive predators, while disadvantaging their medium-sized native mammalian prey. Further replication and longer-term experiments are needed before these findings can be generalized. Nonetheless, such interactions could pose a serious threat to vulnerable species such as critical weight range mammals. Integrated invasive predator and fire management are recommended to improve biodiversity conservation in flammable ecosystems.