In Lake Erie and Lake Ontario, the Ponto-Caspian amphipod Echinogammarus ischnus has replaced the native amphipod Gammarus fasciatus on rocky substrates colonized by dreissenid mussels, which provide interstitial refugia for small invertebrates. Based on the premise that an invader's vulnerability to predation is influenced by its evolutionary experience with the predator and its ability to compete for refugia, we hypothesized that amphipod species replacement is facilitated through selective predation by the round goby Neogobius melanostomus, a Ponto-Caspian fish that invaded the Great Lakes in the early 1990s and is now colonizing the St. Lawrence River. In laboratory experiments, we determined if E. ischnus excludes G. fasciatus from mussel patches, and if the vulnerability of G. fasciatus to predation by gobies is increased in the presence of the invasive amphipod. E. ischnus and G. fasciatus did not differ in their use of mussel patches, either when alone or in each other's presence. Both species were equally vulnerable to predation by the round goby. In field experiments, we determined if the round goby exerts a stronger impact than native predators on the relative abundance of amphipod species. Our results suggest that E. ischnus is more vulnerable to native predators, but the round goby does not have a differential impact on the native amphipod. We conclude that competition with E. ischnus does not increase the vulnerability of G. fasciatus to goby predation, and that the round goby does not promote the replacement of G. fasciatus by E. ischnus in the St. Lawrence River. The outcome of antagonistic interactions between exotic and native amphipods is mediated more by abiotic factors than by shared evolutionary history with other co-occurring exotic species.