The growth and photosynthetic responses of microcystin (MC)- and non-MC-producing Microcystis to the submerged macrophyte Myriophyllum spicatum were investigated under plant-Microcystis co-culture conditions (PMC + , PMC-), in comparison with their corresponding mono-culture controls (SMC + , SMC-). The OJIP chlorophyll a fluorescence transient was recorded and analyzed using JIP-test parameters. In comparison with the corresponding mono-culture controls, the quantum efficiencies of the electron transport chain expressed as parameters Ψo and φEo decreased by more than 25% in the PMC- group, much higher than those in the PMC+ group (p < 0.05). The decreasing extent of the electron transport flux ratio ETo/RC was significantly larger in the PMC- group than in the PMC+ group (p < 0.05). The performance index (PIABS) decreased by 26.98% in the PMC- group and by 16.25% in the PMC+ group. These results indicated that the non-MC-producing Microcystis was more sensitive than the MC-producing strain when co-cultured with M. spicatum, and the efficiency and energy flux of electron transport might be the main targets of Photosystem II. Future research should focus on the intraspecific composition and toxigenic levels of Microcystis populations interacting with submerged macrophytes to guide the use of submerged vegetation restoration.