Global biodiversity is lost at an unprecedented ratio driven by climate change and land-use change. However, little is known about the combined effects of climate and land-use change on future biodiversity on a global scale. Here, we first build the indices of land-use naturalness and the land-use intensity to depict the land-use change on a global scale. By using random forest models, we establish the empirical relationship to quantify this combined effect and further predict future changes of terrestrial vertebrates can be predicated under the Shared Socio-economic Pathways (SSPs). The relative contributions of climate change and land-use change to terrestrial vertebrates are finally separated through quantitative analysis. We find that future land-use change contributes to 48.52% of richness changes, slightly lower than that of climate change. Nearly 45.82% of the Earth’s land will suffer richness losses of terrestrial vertebrates by 2050 even under the middle-high scenario of SSP3, mainly located at low latitudes, such as Southeast Asia, Latin America and sub-Saharan Africa. Moreover, the analysis at the country-specific level reveals that nearly half of the world’s countries would experience species richness loss in the nearby future. These findings make clear that both climate change and land-use change pose comparably significant threats to global biodiversity. More immediate attention and effective actions are urgently needed from local governments for vulnerable regions.