Many contemporary species of large-felids (>15 kg) feed upon prey that are endangered, raising concern that prey population declines (defaunation) will further threaten felids. We assess the threat that defaunation presents by investigating a late Quaternary (LQ), ‘present-natural’ counterfactual scenario. Our present-natural counterfactual is based on predicted ranges of mammals today in the absence of any impacts of modern humans (Homo sapiens) through time. Data from our present-natural counterfactual are used to understand firstly how megafauna extinction has impacted felid communities to date and secondly to quantify the threat to large-felid communities posed by further declines in prey richness in the future. Our purpose is to identify imminent risks to biodiversity conservation and their cascading consequences and, specifically, to indicate the importance of preserving prey diversity. We pursue two lines of enquiry; first, we test whether the loss of prey species richness is a potential cause of large-felid extinction and range loss. Second, we explore what can be learnt from the large-scale large-mammal LQ losses, particularly in the Americas and Europe, to assess the threat any further decline in prey species presents to large-felids today, particularly in Africa and Asia. Large-felid species richness was considerably greater under our present-natural counterfactual scenario compared to the current reality. In total, 86% of cells recorded at least one additional felid in our present-natural counterfactual, and up to 4-5 more large-felids in 10% of the cells. A significant positive correlation was recorded between the number of prey species lost and the number of large-felids lost from a cell. Extant felids most at risk include lion and Sunda clouded leopard, as well as leopard and cheetah in parts of their range. Our results draw attention to the continuation of a trend of megafauna decline that began with the emergence of hominins in the Pleistocene.