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Accelerating climate and land‐use change are rapidly transforming Earth's biodiversity. While there is substantial evidence on the exposure and vulnerability of biodiversity to global change at the species level, the global exposure of intraspecific genetic diversity (GD) is still unknown. Here, we assess the exposure of mitochondrial GD to mid‐21st century climate and land‐use change in terrestrial mammal assemblages at grid‐cell and bioclimatic region scales under alternative narratives of future societal development. We used global predictions of mammal GD distribution based on thousands of georeferenced mitochondrial genes for hundreds of mammal species, the latest generation of global climate models from the ongoing sixth phase of the Coupled Model Intercomparison Project (CMIP6), and global future projections of land‐use prepared for CMIP6. We found that more than 50% of the genetically poorest geographic areas (grid‐cells), primarily distributed in tundra, boreal forests/taiga and temperate bioclimatic regions, will be exposed to mean annual temperature rise that exceeds 2°C compared to the baseline period under all considered future scenarios. We also show that at least 30% of the most genetically rich areas in tropical, subtropical and montane regions will be exposed to an increase of mean annual temperature > 2°C under less optimal scenarios. Genetic diversity in these rich regions is also predicted to be exposed to severe reductions of primary vegetation area and increasing human activities (an average loss of 5–10% of their total area under the less sustainable land‐use scenarios). Our findings reveal a substantial exposure of mammal GD to the combined effects of global climate and land‐use change. Meanwhile the post‐2020 conservation goals are overlooking genetic diversity, our study identifies both genetically poor and highly diverse areas severely exposed to global change, paving the road to better estimate the geography of biodiversity vulnerability to global change. [ABSTRACT FROM AUTHOR]