Ultrasound can inhibit cyanobacterial growth through rupturing cells, but this pathway frequently has the risk to release intercellular toxin (e.g., microcystin). Depressing photosynthesis without cell disruption may provide a new strategy to control cyanobacterial blooms using ultrasound, especially Microcystis blooms. In this work, Microcystis aeruginosa (toxic cyanobacteria) and Chlorella pyrenoidosa (typical green algae) were chosen as model microalgae to verify this hypothesis. Results showed that ultrasound has the ability to inhibit cyanobacterial photosynthesis significantly and selectively. Specifically, sonication damaged QA, a tightly bound one-electron acceptor, and blocked electron flow at QB, a two-electron acceptor, in the photosystem II (PSII) of M. aeruginosa when it was exposed for 60 s (35 kHz, 0.043 W/cm3). Moreover, 44.8% of the reaction centers (RCs) in the PSII of M. aeruginosa were transferred into inactive ones (RCsis), and the cell concentration decreased by 32.5% after sonication for 300 s. By contrast, only 7.9% of RCsi occurred in C. pyrenoidosa, and cell concentration and chlorophyll-a content reduced by 18.7% and 9.3%, respectively. Differences in both species (i.e., cell structures) might be responsible for the varying levels to sonication. This research suggests that cyanobacteria, especially Microcystis, could be controlled by ultrasound via damaging their PSIIs.