Freshwater cyanobacterial blooms (e.g., blooms) constitute a major global environmental problem because of their risks to public health and aquatic ecological systems. Current physicochemical treatments of toxic cyanobacteria cause the significant release of cyanotoxin microcystins from damaged cells. Biological control is a promising eco-friendly technology to manage harmful cyanobacteria and cyanotoxins. Here, we demonstrated an efficient biological control strategy at the laboratory scale to simultaneously remove and microcystins via the combined use of the algicidal bacterial filtrate and the microcystin-degrading enzymatic agent. The algicidal indigenous bacterium sp. SJ-73 was isolated from the sediment of northern Lake Taihu, China, and the microcystin-degrading enzymatic agent (MlrA) was prepared via the heterologous expression of the gene in the indigenous microcystin-degrading bacterium sp. HW isolated from Lake Taihu. The single use of a fermentation filtrate (5%, /) of sp. SJ-73 for seven days removed the unicellular PCC 7806 and the native colonial strain TH1701 in Lake Taihu by 84% and 92%, respectively, whereas the single use of MlrA removed 85% of microcystins. Used in combination, the fermentation filtrate and MlrA removed TH1701 and microcystins by 92% and 79%, respectively. The present biological control thus provides an important technical basis for the further development of safe, efficient, and effective measures to manage blooms and microcystins in natural waterbodies.