In Mediterranean systems, such as south-east Australia, predictions of climate change including lower rainfall and extended drought, threaten vulnerable mammal species. We investigated the relationship between rainfall and population dynamics for a native rodent at risk of extinction, the New Holland mouse (Pseudomys novaehollandiae). In the eastern Otways, the species was significantly influenced by rainfall, exhibiting a population irruption (15–20 individuals ha^–1) following six years of above-average rainfall and a precipitous decline to site extinction during subsequent drought. The decline was predominantly related to loss of adults before and during breeding seasons, together with an apparent decrease in juvenile survival. Population abundance was positively correlated with a rainfall lag of 0–9 months. We propose that the response of this omnivore to high rainfall was mediated through increased productivity and that rainfall decline resulted in resource depletion and population decline. Under a drying climate the direct impacts of rainfall decline will continue. However management of other threats may increase the species’ resilience. Burning to provide optimal successional vegetation, protection of refugia, and predator control are priorities. However, burning should be avoided during drought, as the likelihood of local extinctions is substantial.