Inland fisheries often receive little to no attention in global discussions about sustainable development. The consequences of overlooking inland fisheries in sustainability dialogues are increasingly problematic as fisheries stressors (e.g., overharvest, species invasion, climate change, habitat modification) intensify. Elevating the global profile of inland fisheries requires an approach for quantifying and clearly conveying the ecological, economic, and societal values of these systems. One such approach involves the Blue Economy, a multifaceted concept initially used to describe the intersection of marine conservation and sustainable use of marine resources for economic growth. Although conceptually powerful, the Blue Economy has rarely been applied to inland waters and fisheries. To address this knowledge gap, we conceptualized Laurentian Great Lakes fisheries from a Blue Economy perspective. In particular, we evaluated the utility of the coupled human and natural systems (CHANS) framework for characterizing the ecological, economic, and societal values of Laurentian Great Lakes fisheries and associated contributions to the Blue Economy (e.g., human livelihoods, food security, recreation, conservation, economic prosperity). There are numerous opportunities to leverage CHANS methods (e.g., metacoupling, telecoupling) and associated mathematical models to advance fisheries science, inform fisheries management, and ultimately move toward a Blue Economy in the Laurentian Great Lakes. To that end, we demonstrated applications of CHANS methods, discussed strategies for communicating with stakeholders, and provided insights for navigating challenges to developing a Blue Economy in the Laurentian Great Lakes—a model that could be used in the African Great Lakes and other large ecosystems in the world.