In order to deactivate food-borne pathogens, such as E. coli O157: H7, in water, E. coli bactericidal testing was conducted using pulsed discharge plasma, continuous wave (CW) discharge plasma, and a hybrid discharge of both pulsed and CW plasma. The pulsed discharge instantaneously destroyed the E. coli cell wall by the shock wave and the UV radiation generated by the 10 MJ of pulse energy, while the CW discharge plasma sterilized the E. coli by free available chlorines (FAC), oxidizing agents, and active species. We determined the best disinfection conditions so that the hybrid discharge plasma could kill more than 99.9999% of the E. coli within 15 s. The outer wall of the E. coli are damaged by the shockwave generated by the pulsed discharge plasma, which leaves them exposed to attack by the FAC generated by the CW discharge plasma. Transmission Electron Microscope (TEM) images obtained from the cryo-bio-TEM installed at the Korea Basic Science Institute show the E. coli before and after treatment by pulsed plasma, and the damage trends at different time intervals. The E. coli treated for 30 s with the plasma exhibited a rough surface and irregular shape. After 240 s, the outer wall, membrane, and inner cell of the E. coli was destroyed and burst the cell wall. The hybrid plasma system in flowing water would be useful for continuous large-scale water treatment for the purification, sterilization, or disinfection of objects or materials.