The blue crab, Callinectes sapidus Rathbun, 1896, is native to the Atlantic coasts of the Americas and globally one of the most highly invasive marine species. In the present study, the species’ diet and the foraging behaviour was studied in the Thermaikos Gulf and Papapouli Lagoon for the first time. Surveys were undertaken using fyke nets, shore surveys, scuba and snorkelling. Additional data were compiled from systematic interviews with mussel farmers, shellfish traders and fishermen. In both Thermaikos Gulf and Papapouli Lagoon C. sapidus was found to prey on a wide variety of species including economically important molluscs, fishes, and crustaceans, indicating a substantial potential impact on fisheries and aquaculture in the region. Observation showed that over 6 (2009–2014) years, the blue crabs became dominant in Papapouli Lagoon at the expense of the native commercially fished crab Carcinus aestuarii Nardo, 1847 according to fisheries data. Potential management implications are discussed.