AbstractHabitat loss is the greatest threat to biodiversity and rapid, human-forced climate change is likely to exacerbate this. Here we present the first global assessment of current and potential future impacts on biodiversity of a habitat loss and fragmentation–climate change (HLF–CC) interaction. A recent meta-analysis demonstrated that the negative impacts of habitat loss and fragmentation have been disproportionately severe in areas with high temperatures in the warmest month and declining rainfall, although impacts also varied across vegetation types. We compiled an integrated global database of past, current and future climate variables and past vegetation loss to identify ecoregions where (i) past climate change is most likely to have exacerbated the impacts of HLF, and (ii) forecasted climate change is most likely to exacerbate the impacts of HLF in the future. We found that recent climate change is likely (probability >66%) to have exacerbated the impacts of HLF in 120 (18.5%) ecoregions. Impacted ecoregions are disproportionately biodiverse, containing over half (54.1%) of all known terrestrial amphibian, bird, mammal, and reptile species. Forecasts from the RCP8.5 emissions scenario suggest that nearly half of ecoregions globally (n=283, 43.5%) will become impacted during the 21st century. To minimize ongoing and future HLF–CC impacts on biodiversity, ecoregions where impacts are most likely must become priorities for proactive conservation actions that avoid loss of native vegetation (e.g., protected area establishment). Highly degraded ecoregions where impacts are most likely should be priorities for restoration and candidates for unconventional conservation actions (e.g. translocation of species).