In the autumn of 2006, the freshwater hydrozoan jellyfish Craspedacusta sowerbii was observed for the first time in a small lake in Louisville, Kentucky, USA. Medusae were collected for two experiments involving the prey items Bosmina longirostris, Daphnia magna and Daphnia lumholtzi, and for a third experiment in unfiltered pond water containing natural densities of in situ fauna. Medusa presence significantly increased prey mortality for all three species in the first two experiments. We found that B. longirostris and D. lumholtzi were significantly more likely to be consumed once killed, compared to D. magna. Daphnia magna was killed at a high rate, but was not consumed. When placed in whole pond water containing a natural complement of zooplankton, medusae were found to significantly alter community abundance by reducing the population abundance of many of the common zooplankton species present, including the rotifer Ascomorpha spp., copepod adults and nauplii, and B. ongirostris. We argue that C. sowerbii presence has the potential to significantly alter zooplankton communities and, therefore, aquatic food webs, via both direct predation (rotifers, small cladocera, copepods) and incidental mortality (larger zooplankton and small/larval fish).