AbstractClimate change is increasing variability in precipitation patterns in many parts of the globe. Unpredictable changes in water availability can be particularly challenging for organisms that rely on precipitation‐fed water sources for completing their life cycle, such as many amphibian species. Although developmental plasticity can mitigate the impacts of changing environments for some species, this strategy can come at a cost to other fitness‐linked traits, such as immune function. We investigated localized variation in the capacity to respond to pond drying and evaluated whether developmental responses induced carry‐over effects in disease susceptibility in three leopard frog species (Rana [Lithobates] pipiens and Rana sphenocephala; two populations each, and one population of Rana chiricahuensis). Using mesocosms located near the site of collection (<15 km away) in five regions spanning a latitudinal gradient, we raised tadpoles under simulated fast drying, slow drying, or constant water levels. After metamorphosis, we characterized several aspects of the skin microbiome, immune function, and response to exposure to the fungal pathogen Batrachochytrium dendrobatidis (Bd). Note that for R. chiricahuensis, the only carry‐over effect measured was response to Bd exposure, for which we observed no effects of pond drying. We found that developmental plasticity in response to drying was rare, except in the southernmost population of R. sphenocephala. In this location, tadpoles responded by accelerating development, and frogs with shorter larval periods developed more severe infections following Bd exposure post‐metamorphosis, suggesting a trade‐off between surviving pond drying and pathogen defense investment. In the three other locations, a lack of accelerated metamorphosis in drying treatments was accompanied by increased mortality, decreased anti‐Bd function of the microbiome, and/or greater Bd infection after exposure. Overall, results suggest that faster drying conditions will likely have negative impacts on amphibians with long larval periods, both directly and indirectly via carry‐over effects. Because effects of drying exposure were not uniform within a species, our findings suggest that local responses may not be generalizable to other regions of the range. These multifaceted effects of climate change on pathogen defenses are increasingly relevant as emerging infectious diseases threaten global biodiversity.