Human-induced environmental and climate change are widely blamed for causing rapid global biodiversity loss, but direct estimation of the proportion of biodiversity lost at local or regional scales are still infrequent. This prevents us from quantifying the main and interactive effects of anthropogenic environmental and climate change on species loss. Here, we demonstrate that the estimated proportion of species loss of 252 key protected vertebrate species at a county level of China during the past half century was 27.2% for all taxa, 47.7% for mammals, 28.8% for amphibians and reptiles and 19.8% for birds. Both human population increase and species richness showed significant positive correlations with species loss of all taxa combined, mammals, birds, and amphibians and reptiles. Temperature increase was positively correlated with all-taxa and bird species loss. Precipitation increase was negatively correlated with species loss of birds. Human population change and species richness showed more significant interactions with the other correlates of species loss. High species richness regions had higher species loss under the drivers of human environmental and climate change than low-richness regions. Consequently, ongoing human environmental and climate changes are expected to perpetuate more negative effects on the survival of key vertebrate species, particularly in high-biodiversity regions.