Interactions of cold atmospheric-pressure plasma jets (APPJs) and water are important for water purification, chemical synthesis, medicine, and biotechnology. However, the reactivity and bactericidal effects of water activated with jets of different ionized gases remain unclear, especially in the commonly used helium (He)- and argon (Ar)-APPJ systems. Here, He and Ar are used as working gases to produce APPJ for comparing the plasma-induced aqueous reactive species and bacteria inactivation effects in solutions. Experimental results indicate that the Ar plasma jet shows a quicker propagation velocity and higher concentrations of gaseous reactive species, and the gas and electron temperature are different for the He and Ar plasma. Moreover, the higher concentration of aqueous reactive species, such as ∙OH, ∙O2−/ONOOH, H2O2, NO2−, and NO3−, and better bacterial inactivation effects are achieved by the Ar plasma treatment. Water deformation induced from plasma water is found as the reason for the different reactivity and bactericidal effects. Further validation experiments using a film with different pore diameters confirm that the molecular weight of the working gas influences the shape and stability of the cavity induced by the gas flow in the plasma jet, and plays a vital role in the production of aqueous reactive species with variable concentrations.