Aetokthonos hydrillicola (Ah) is a newly described cyanobacteria that forms dense colonies on aquatic macrophytes, primarily invasive Hydrilla verticillata, and is associated with mortality of freshwater wildlife. Prior research shows that Ah growing on Hydrilla is potently toxic to waterbirds, turtles, and fish, suggesting potentially broad sensitivity among vertebrates. We tested whether amphibian tadpole species were affected by ingestion of Ah-positive Hydrilla, and whether season, host plant, or tadpole age/size affected tadpole vulnerability. For trials involving ranid tadpoles (Bullfrogs, Rana catesbeiana; Green frogs, R. clamitans; and Southern leopard frogs, R. sphenocephala), feeding on Ah-positive Hydrilla collected during October–November resulted in the development of lesions within brain tissue and significant mortality. Ranid tadpole sensitivity to Ah toxin did not vary with age or size, but vulnerability from ingestion of Ah-positive Hydrilla varied seasonally and between two syntopic host plants. An unexpected result of our study was the apparent insensitivity of Green treefrog tadpoles (Hyla cinerea) fed toxic, Ah-positive Hydrilla. In conjunction with other studies, our results confirm wide but variable sensitivity among major vertebrate lineages to the Ah toxin. Differential sensitivity among species means that the introduction of Ah could alter interactions and structure within aquatic communities.