Freshwater mussels (Family: Unionidae) and their fish hosts are highly diverse and interdependent taxa with contrasting life history strategies. These strategies, categorized within a triangular framework (opportunistic, periodic, equilibrium), reflect differences in reproductive patterns, growth rates, and life expectancy, and predict species distributions and habitat preferences under varying environmental conditions. Mussels rely on an obligate ectoparasitic larval stage on host fish, making host-parasite interactions fundamental to their ecology. This study integrates life history traits, host fish associations, and presence/absence datasets to examine the relationships between 169 mussel species and 279 fish species across North America, with a focus on the Southeast U.S. Our findings reveal an inverse relationship between mussel and host life history strategies. Equilibrium mussels predominantly utilize opportunistic fish hosts, while opportunistic mussels rely on equilibrium fish species. Leuciscidae (minnows) emerged as key hosts for equilibrium mussels, particularly species within the genus Cyprinella. Opportunistic mussels were most frequently associated with Centrarchidae (sunfishes), especially the genus Lepomis, while periodic mussels primarily relied on Percidae (perches), with Etheostoma being the most common host genus. Additionally, watersheds with higher proportions of equilibrium fishes tended to host fewer equilibrium mussels, and those with more opportunistic mussels supported fewer opportunistic fish. By integrating host-parasite dynamics within a life history strategy framework, this study provides critical insights into the ecological interdependence of freshwater mussels and their fish hosts. These findings offer a foundation for developing integrated co-management approaches, representing an essential step toward holistic conservation strategies for these imperiled freshwater taxa.