The high dependence on plastics in Ghana has resulted in the generation of large quantities of plastic waste which are poorly managed and improperly disposed into the aquatic environments. This study assessed the spatial distribution and abundance of microplastics in mangrove oysters (Crassostrea tulipa): a major fishery resource of commercial importance in Ghana. The results showed that 84.0% of all individuals examined had ingested microplastics. A total of 276 microplastic items were recovered from the 120 individual oysters. Densu (100%) and Volta (93%), two estuaries situated in urban areas, had a greater incidence of microplastics than Whin (77%) and Nakwa (66%), estuaries situated in peri-urban and rural settlements, respectively. The mean microplastic abundance ranged from 1.4 to 3.4 items/individual and 0.34 to 1.7 items/g tissue wet weight. Fiber accounted for 69% of microplastic shapes, followed by fragments (27%) and films (4%). Polymer analysis showed polyethylene (PE), polypropylene (PP) and polystyrene (PS) as the most common types in oysters. The estimated microplastic intake per capita per year was one magnitude higher than the mean for other countries. This high rate of human exposure to microplastics requires an eminent policy formulation to guide the use, management and disposal of plastic waste in Ghana.