In this paper, the chemical and physical effects generated during the dielectric barrier discharge plasma (DBDP) process, including O₃, H₂O₂, light, e*, etc., were utilized to activate the peroxydisulfate (PDS) to form SO₄−•. Then, the original reactive oxygen species (ROS), such as •OH, formed in the discharge system was combined to degrade the enrofloxacin (ENR) in water, and the corresponding influencing parameters and reactive substance in the DBDP/PDS system were analyzed. From the investigation, it was found that the neutral (pH =6.5) solution was more conducive to the ENR decomposition than the acidic and alkaline solution conditions. The presence of Fe2+ and Cu2+ in the reaction solution could hasten the ENR degradation, whereas the addition of Cl− and the HCO₃− in the solution had a negative effect. Analysis of the reactive species and quenching tests were carried out to explore the generation of H₂O₂, O₃, •OH, and SO₄−• in the DBDP/PDS system and their effects on the ENR degradation. The UV-Vis and 3D fluorescence spectra analysis were applied to demonstrate the cooperative effects of the DBDP and the PDS. The TOC and COD removals of the ENR solutions in the DBDP and the DBDP/PDS systems were also compared. Based on the intermediates analysis of the ENR degradation, three possible pathways of ENR decomposition in the synergistic system have been inferred.