Fire has been a source of global biodiversity for millions of years. Yet, interactions with anthropogenic drivers such as climate change, land-use and invasive species are changing the nature of fire activity and its impacts. We review how such changes are threatening species with extinction and transforming terrestrial ecosystems. Conservation of Earth’s biological diversity will be achieved only by recognizing and responding to the critical role of fire. In the Anthropocene, this requires that conservation planning explicitly include the combined effects of human activities and fire regimes. Improved forecasts for biodiversity must also integrate the connections between people, fire and ecosystems. Such integration provides an opportunity for new actions that could revolutionize how society sustains biodiversity in a time of changing fire activity.