The catch per unit effort (CPUE), population structure, sex ratio, and reproductive aspects of the invasive blue crab Callinectes sapidus Rathbun were studied in Monolimni Lagoon and the adjacent coastal waters in the estuarine area of the Evros River (Northeast Aegean Sea, Eastern Mediterranean). The CPUE varied both seasonally and spatially; higher values were recorded in summer and fall in the lagoonal stations characterized by shallow depth (<0.5 m) and a dense meadow of the angiosperm Ruppia maritima, whereas significantly lower CPUE was recorded in the adjacent coastal area. The bottom temperature was positively correlated with CPUE. Μodal progression analysis estimated a three-modal size–frequency distribution for both sexes corresponding to the 0⁺, 1⁺, and 2⁺ age classes. Females attained a significantly larger size (carapace width (CW)) than males. Crab size decreased from the marine area to the lagoonal stations. The sex ratio was estimated at 2.45:1 (♂/♀). Males dominated in all months, except for October, when an equal sex ratio was observed. The mean size at maturity (L₅₀) of females was estimated at 124 mm CW. Females with mature ovaries were found from February to October. Ovigerous females were observed from May to October in the coastal area, where a spawning peak occurred in September. In the Evros River estuary, the American blue crab exhibits a life cycle that seems to conform to the general complex life-cycle pattern of the species along the mid-Atlantic coast.