Crustaceans, mollusks, and fish are wetland resources that constitute an important source of protein and foreign exchange for the Ghanaian population, and many species of these are sold in the open market and restaurants, yet studies on their heavy metal contents are generally scarce. This paper evaluates the levels of mercury in five species of crustaceans, two species of mollusks, and ten species of fish inhabiting three river basins with different catchment activities in Ghana. These include the Ankobra Basin, characterized with mining and agriculture, Densu Basin, associated with urban waste discharges and agriculture, and Lower Volta River Basin, associated with agricultural activities. Mercury concentration was highest in Ankobra (2.5 ± 2.59 μg g⁻¹) followed by Densu (1.75 ± 1.35 μg g⁻¹) and Volta (0.74 ± 1.46 μg g⁻¹). The mercury load of the organisms range from <0.1 to 4 μg g⁻¹ with the highest load in Cynoglossus senegalensis at Ankobra. Except for Panaeus notialis from Densu and Ankobra, and three other species from Ankobra (Tympanotonus fuscatus, Cardisoma armatum, Callinectes amnicola) in which mercury was not detected, mercury loads of all the organisms were above the permissible limit of 0.5 mg kg⁻¹ established by Commission Regulation-EC (2006) for fishery products and muscle meat of fish. Weekly quantities of crustaceans and mollusks considered safe for consumption by adults ranged from 88 and 1000 g while that of the fishes were between 70 and 700 g (on a dry weight basis) depending on the species. It was clear that some caution needs to be exercised in the consumption of Ghana’s fresh and brackish water fisheries.