Significance: Despite the critical threat of habitat fragmentation, global patterns of fragmentation and its relationship to extinction risk have not been quantified for any major taxon. We developed high-resolution models that provide a global assessment of the degree of habitat fragmentation impacting the world’s terrestrial mammals. Results demonstrate that mammals with more fragmentation are at greater risk of extinction, even after accounting for the effects of key macroecological predictors, such as body size and geographic range size. Species with higher fragmentation had smaller ranges and a lower proportion of high-suitability habitat within their range, and most high-suitability habitat occurred outside of protected areas, further elevating extinction risk. Quantification of habitat fragmentation will help guide strategic priorities for global mammal conservation.