The electro-peroxone (EP) process is an electricity-based oxidation process enabled by electrochemically generating hydrogen peroxide (H2O2) from cathodic oxygen (O2) reduction during ozonation. In this study, the removal of antibiotic resistant bacteria (ARB) and plasmid-encoded antibiotic resistance genes (ARGs) during groundwater treatment by ozonation alone and the EP process was compared. Owing to the H2O2-promoted ozone (O3) conversion to hydroxyl radicals (•OH), higher •OH exposures, but lower O3 exposures were obtained during the EP process than ozonation alone. This opposite change of O3 and •OH exposures decreases the efficiency of ARB inactivation and ARG degradation moderately during the EP process compared with ozonation alone. These results suggest that regarding ARB inactivation and ARG degradation, the reduction of O3 exposures may not be fully counterbalanced by the rise of •OH exposures when changing ozonation to the EP process. However, due to the rise of •OH exposure, plasmid DNA was more effectively cleaved to shorter fragments during the EP process than ozonation alone, which may decrease the risks of natural transformation of ARGs. These findings highlight that the influence of the EP process on ARB and ARG inactivation needs to be considered when implementing this process in water treatment.