The discharge of aquaculture wastewater increased significantly in China. Especially, high content of nitrogen and phosphorus in wastewater could destroy the receiving water environment. To reduce the pollution of aquaculture wastewater, farmed triangle sail mussel (Hyriopsis cumingii) was proposed to be cultivated in the river. This was the first time that bacteria (Bacillus subtilis and Bacillus licheniformis) and microalgae (Chlorella vulgaris) were also used and complemented ecosystem functions. The pollutants in wastewater were assimilated by Chlorella vulgaris biomass, which was then removed through continuous filter-feeding of Hyriopsis cumingii. While, Bacillus subtilis and Bacillus licheniformis enhanced the digestive enzyme activities of mussel. It demonstrated that approximately 4 mussels/m3 was the optimal breeding density. Under such condition, orthogonal experiment indicated that the dose of Bacillus subtilis, Bacillus licheniformis, and Chlorella vulgaris should be 0.5, 1, and 2 mL respectively. Compared with mussel, mussel/microalgae, mussel/bacteria system, treatment ability of the mussel/microalgae/bacteria system in batch experiment was better, and 94.67% of NH3-N, 92.89% of TP and 77.78% of COD were reduced after reaction for 6 days. Finally, 90 thousand mussels per hectare of water were cultivated in Kulv river in China, and the field experiment showed that water quality was significantly improved. After about 35 days of operation, NH3-N, TN, TP and COD concentration were maintained around 0.3, 0.8, 0.3, and 30 mg/L respectively. Therefore, the mussel/microalgae /bacteria system in this study showed a sustainable and efficient characteristic of aquaculture wastewater bioremediation.