Fish is an important source of nutritional omega-3 (n-3) polyunsaturated fatty acids, but it also readily accumulates toxic mercury (Hg) and microcystins (MC) in eutrophic aquatic systems. In China, farmed fish was widely consumed, and aquaculture has caused pervasive eutrophication of freshwater lakes, resulting in the increasing accumulation of MC in fish tissue. To assess the risk-benefit of consuming farmed fish, 205 fish samples of 10 primary species were collected from the eutrophic Wujiangdu (WJD) Reservoir, SW China. The contents of Hg, microcystin-RR (MC-RR), microcystin-LR (MC-LR), and polyunsaturated fatty acids (PUFA) in fish were analyzed. The results showed that THg and MeHg concentrations in all fish sampls were well below the safety limit (500 ng/g w.w) established by the Standardization Administration of China, with average values of 22.9 ± 22.8 and 6.0 ± 6.6 ng/g wet weight (w.w.), respectively. Average concentrations of MC-RR and MC-LR were 40 ± 80 and 50 ± 80 ng/g w.w., respectively. MC-RR and MC-LR concentrations in fish were significantly higher in silver carp and black carp than in perch and catfish (p < 0.05). In nutritional terms, average concentrations of n-3 PUFA and the eicosapentaenoic (EPA) + docosahexaenoic acids (DHA) of fish were 2.0 ± 2.5 and 1.4 ± 0.5 mg/g w.w., respectively. The risk-benefit assessment suggests that the n-3 PUFA benefits from consuming all farmed fish species in the WJD Reservoir outweigh the adverse effects of MeHg. However, except for perch, most fish species still pose a high MC-LR exposure risk that created a requirement for fish consumption advisories and monitoring. Consequently, more attention should be paid on the health risk of combined exposure to pollutants by aquatic product consumption.