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Climate and land cover change are driving a major reorganization of terrestrial biotic communities in tropical ecosystems. In an effort to understand how biodiversity patterns in the tropics will respond to individual and combined effects of these two drivers of environmental change, we use species distribution models (SDMs) calibrated for recent climate and land cover variables and projected to future scenarios to predict changes in diversity patterns in Madagascar. We collected occurrence records for 828 plant genera and 2186 plant species. We developed three scenarios, (i.e., climate only, land cover only and combined climate-land cover) based on recent and future climate and land cover variables. We used this modelling framework to investigate how the impacts of changes to climate and land cover influenced biodiversity across ecoregions and elevation bands. There were large-scale climate- and land cover-driven changes in plant biodiversity across Madagascar, including both losses and gains in diversity. The sharpest declines in biodiversity were projected for the eastern escarpment and high elevation ecosystems. Sharp declines in diversity were driven by the combined climate-land cover scenarios; however, there were subtle, region-specific differences in model outputs for each scenario, where certain regions experienced relatively higher species loss under climate or land cover only models. We strongly caution that predicted future gains in plant diversity will depend on the development and maintenance of dispersal pathways that connect current and future suitable habitats. The forecast for Madagascar's plant diversity in the face of future environmental change is worrying: regional diversity will continue to decrease in response to the combined effects of climate and land cover change, with habitats such as ericoid thickets and eastern lowland and sub-humid forests particularly vulnerable into the future.