As a vital source of nutrition, cultural identity, and economic activity, seafood has become one of the most globally traded commodities worldwide. However, increased concerns about food security, coupled with the disruptive effects of climate change, contagious diseases, and geopolitical conflict are bringing acute attention to the need for food transformation at multiple scales. Here, we investigate the United States’ potential to achieve seafood “independence” and maximize health benefits to the nation by integrating production, utilization, yield, and consumption data across six regions of the United States and nationally over 50 years (1970-2021). Although the United States is the second largest importer of seafood worldwide, findings from this study show that self-reliance at the national-level is achievable, though the ability for different subregions to meet demand is variable. Achieving greater seafood independence will require shifts in consumer behavior, investments in infrastructure, and continual adaptation in the face of climate change.