The rise of humanity to ecological dominance has precipitated concerted patterns of environmental change across every biome on Earth. Human activities can upend the adaptive landscapes on which species' have evolved, causing the sudden maladaptation of lineages to these novel conditions. Amphibians are amongst the most threatened vertebrates, with contemporary extinctions driven by multiple interacting stressors including habitat destruction, introduced pathogens, and climate change. Despite these looming threats, we understand little about how or why susceptibility to these stressors varies across amphibian lineages. In this thesis, I investigate the evolutionary origins of modern extinction risk in the Amphibia, by examining comparative patterns of susceptibility to various drivers of extinction. First, I show that modern extinction risk positively covaries with speciation rates across amphibian genera due to the most rapidly-diversifying clades producing numerous range-restricted and vulnerable species. Second, I demonstrate how evolutionary dynamics may influence local-scale extinction by examining amphibian species' responses to deforestation across the world. Contrary to patterns of global threat, the slowest-diversifying amphibian lineages are disproportionately lost from human-modified ecosystems - which may reflect a relationship between diversification and niche lability. Third, I examine phylogenetic and trait-based patterns of susceptibility to a human-dispersed fungal pathogen. Though species' ecology and life history consistently shape infection patterns across diverse amphibian assemblages, these traits appear to bear little weight for species' extinction risk from disease epidemics. Fourth, I test the relative effects of both dehydration and temperature on performance, and therefore climate risk, in three ecologically diverse anuran species. Performance was maintained across broad thresholds of dehydration in all species, but warmer temperatures accelerated the onset of performance decline. Species-specific biophysical modelling revealed stark differences in how dehydration is likely to limit activity in each species, suggesting that desiccation physiology may be an important driver of extinction risk from climate change in amphibians. These studies collectively illustrate that amphibian species' responses to anthropogenic environmental change have deep evolutionary roots. In turn, we can expect our continued environmental dominance to fundamentally reshape the evolutionary tree of amphibians into the future.