Climate change will decrease worldwide biodiversity through a number of potential pathways1, including invasive hybridization2 (cross-breeding between invasive and native species). How climate warming influences the spread of hybridization and loss of native genomes poses difficult ecological and evolutionary questions with little empirical information to guide conservation management decisions3. Here we combine long-termgenetic monitoring data with high-resolution climate and stream temperature predictions to evaluate how recent climate warming has influenced the spatiooral spread of human-mediated hybridization between threatened native westslope cutthroat trout (Oncorhynchus clarkii lewisi) and non-native rainbow trout (Oncorhynchus mykiss), the worlds most widely introduced invasive fish4. Despite widespread release of millions of rainbow trout over the past century within the Flathead River system5, a large relatively pristine watershed in western North America, historical samples revealed that hybridization was prevalent only in one (source) population. During a subsequent 30-year period of accelerated warming, hybridization spread rapidly and was strongly linked to interactions between climatic drivers-precipitation and temperature-and distance to the source population. Specifically, decreases in spring precipitation and increases in summer stream temperature probably promoted upstream expansion of hybridization throughout the system. This study shows that rapid climate warming can exacerbate interactions between native and non-native species through invasive hybridization, which could spell genomic extinction for many species.