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Despite increasing efforts globally to remove dams and construct fish passage structures, broad-scale analyses balancing tradeoffs between cost and habitat gains from these mitigations infrequently consider invasive species. We present an optimization-based approach for prioritizing dam mitigations to restore habitat connectivity for native fish species, while limiting invasive species spread. Our methodology is tested with a case study involving 240 dams in the Upper Mississippi River, USA. We integrate six native migratory fish species distribution models, distributions of two invasive fishes, and estimated costs for dam removal and construction of fish passes. Varying budgets and post-mitigation fish passage rates are analyzed for two scenarios: ‘no invasives’ where non-selective mitigations (e.g., dam removal) are used irrespective of potential invasive species habitat gains and ‘invasives’ where a mixture of selective (e.g., lift-and-sort fish passage) and non-selective mitigations are deployed to limit invasive species range expansion. To achieve the same overall habitat connectivity gains, we find that prioritizations accounting for invasive species are 3 to 6 times more costly than those that do not. Habitat gains among native fish species were highly variable based on potential habitat overlap with invasive species and post-mitigation passabilities, ranging from 0.4–58.9% (‘invasives’) and 7.9–95.6% (‘no invasives’) for a $50M USD budget. Despite challenges associated with ongoing nonnative fish invasions, opportunities still exist to restore connectivity for native species as indicated by individual dams being frequently selected in both scenarios across varying passabilities and budgets, however increased restoration costs associated with invasive species control indicates the importance of limiting their further spread within the basin. Given tradeoffs in managing for native vs. invasive species in river systems worldwide, our approach demonstrates strategies for identifying a portfolio of candidate barriers that can be investigated further for their potential to enhance native fish habitat connectivity while concurrently limiting invasive species dispersal.