Amphibian populations have suffered widespread declines and extinctions in recent decades. Although climatic changes, increased exposure to ultraviolet-B (UV-B) radiation and increased prevalence of disease have all been implicated at particular localities, the importance of global environmental change remains unclear. Here we report that pathogen outbreaks in amphibian populations in the western USA are linked to climate-induced changes in UV-B exposure. Using long-term observational data and a field experiment, we examine patterns among interannual variability in precipitation, UV-B exposure and infection by a pathogenic oomycete, Saprolegnia ferax. Our findings indicate that climate-induced reductions in water depth at oviposition sites have caused high mortality of embryos by increasing their exposure to UV-B radiation and, consequently, their vulnerability to infection. Precipitation, and thus water depth/UV-B exposure, is strongly linked to El Niño/Southern Oscillation cycles, underscoring the role of large-scale climatic patterns involving the tropical Pacific. Elevated sea-surface temperatures in this region since the mid-1970s, which have affected the climate over much of the world, could be the precursor for pathogen-mediated amphibian declines in many regions.