Disinfection of bacteria-contaminated water is crucial to public health. In this work, a gas-liquid phase air and oxygen plasma is designed to selectively and controllably generate reactive species and efficiently inactivate Staphylococcus aureus (S. aureus) in the liquid. Optical emission spectroscopy (OES) and fluorescent probes are used to analyze the formation of reactive species induced by the plasma in the gas-liquid and liquid phases. OH radicals are observed to be the predominant species in the liquid induced by the oxygen plasma. In the air plasma, owing to the presence of active nitrogen, nitrogen-containing reactive species including NO, HNO2, HNO3, and ONOOH are generated in the liquid. The bactericidal and biological effects associated with the formation of liquid products are investigated. The different bactericidal effects of the air and oxygen plasma (direct and indirect) treatment show that the inactivation efficacy is related to the species and content of the reactive oxygen and nitrogen species produced by the air and oxygen plasma in the liquid. The better inactivation effect of direct oxygen plasma treatment stems from the larger concentration of OH radicals. The presence of active nitrogen, formation of nitrogen-based reactive species, and acidification are responsible for the better bactericidal activity in the air plasma indirect treatment. Cell membrane damage and accumulation of intracellular reactive oxygen species result in inactivation of S. aureus. Selective and more efficient formation of reactive species is attractive to industrial processes such as waste water treatment.