Climate and landcover change can have synergistic impacts on wildlife populations, but the pervasiveness of these threats and factors that buffer them remain unclear despite important implications for conservation. I evaluated the additive and interactive effects of spatiotemporal variation in temperature, precipitation, and landcover change on annual territory occupancy, colonization, and extinction of a threatened toppredator, the ferruginous pygmy-owl (Glaucidium brasilianum), across a vast binational region of the Sonoran Desert over 16 years. I also assessed how local habitat quality and regional population size mediate impacts of these stressors. Despite significant bivariate associations between occupancy and temperature, precipitation, and landcover change, evidence for interactions was much greater than for additive effects. Occupancy of territories imbedded in increasingly disturbed landscapes declined at greater rates with warming winter temperatures, but the temperature had little effect in intact landscapes suggesting they buffer impacts of climate warming. Occupancy increased markedly with precipitation due likely to major positive impacts on prey, but again, interactive effects were stronger given territories of higher quality amplified benefits of precipitation. Impacts of landcover change and habitat quality on extinction depended markedly on regional population sizes. When populations were small and few potential colonists were present, high-quality habitat and low landcover change failed to reduce extinction. When populations were large, however, high-quality habitat and more intact landscapes, which best foster dispersal, reduced extinction. Hence, complex interacting processes linked to the effects of precipitation and habitat quality on carrying capacity, landcover change on habitat connectivity and vulnerability to rising temperatures, and local population sizes simultaneously drove dynamics. Efforts to identify and protect high-quality habitat and limit landcover change can enhance conservation but will be most efficient in intact landscapes. Efforts to enhance local habitat quality and quantity, and directly augment populations should consider broader landscape contexts linked to habitat connectivity and potential source populations.