Copper sulfate is a frequently used reagent for Microcystis blooms control but almost all the previous works have used Microcystis aeruginosa as the target organism to determine dosages. The aim of this study was to evaluate interspecific differences in the responses of various Microcystis species to varying Cu2+ concentrations (0, 0.05, 0.10, 0.25, and 0.50 mg L−1). The half maximal effective concentration values for M. aeruginosa, M. wesenbergii, M. flos-aquae, and M. viridis were 0.16, 0.09, 0.49, and 0.45 mg L−1 Cu2+, respectively. This showed a species-dependent variation in the sensitivity of Microcystis species to copper sulfate. Malonaldehyde content did not decrease with increasing superoxide dismutase content induced by increasing Cu2+, suggesting that superoxide dismutase failed to reduce Cu2+ damage in Microcystis. Considering the risk of microcystin release when Microcystis membranes are destroyed as a result of Cu2+ treatment and the stimulation effects of a low level of Cu2+ on growth in various species, our results suggest that copper sulfate treatment for Microcystis control could be applied before midsummer when M. aeruginosa and M. viridis are not the dominant species and actual amount of Cu2+ used to control M. wesenbergii should be much greater than 0.10 mg L−1.