jabbrv-ltwa-all.ldf jabbrv-ltwa-en.ldf Understanding the processes that drive spatial genetic differentiation is essential for understanding how populations adapt to environmental change. By evaluating the relative influence of these drivers, we can gain insights into evolutionary dynamics and the potential for species to respond to shifting landscapes. Three well-accepted drivers of spatial patterns in genetic variation are isolation-by-distance (IBD), where individuals are more genetically similar the closer they are geographically; isolation-by-environment (IBE), where gene flow is reduced due to selection against migrants in unsuitable ecological conditions; and isolation-by-resistance (IBR), where landscape features limit dispersal. We employed a macrogenetic approach, conducting a multi-species, multi-driver, meta-analysis of published genomic SNP data to identify general patterns driving spatial genetic differentiation of mammals globally. Three species distribution models were built per species to test different aspects of IBR, using combinations of landscape and bioclimatic variables. Using two model selection techniques, we find that landscape resistance models better explain genetic differentiation than bioclimatic resistance models. Among the three drivers, IBR was most frequently selected as the best model of genetic differentiation in mammals across both model selection tests, with IBD a close second and IBE the worst performing model. However, the importance of IBE increased with increasing spatial scale, with populations spread over larger distances more likely to be diverging due to IBE than IBR or IBD. Our findings suggest that anthropogenic habitat fragmentation significantly shapes genetic variation in mammals worldwide, underscoring the importance of mitigating the impacts of habitat fragmentation to prevent isolation and extinction of mammalian species.