Antibiotic pollution has become one of the most challenging environmental issues in aquatic ecosystems, with adverse effects on human health. It is imperative to develop efficient technologies to degrade antibiotics in water to ensure environmental safety. In this study, a novel, efficient, and environmentally friendly method combining peracetic acid with dielectric barrier discharge (PAA/DBD) was developed to degrade sulfamethoxazole (SMX) in wastewater. The combination of PAA and DBD had significant synergistic effects on SMX decomposition with a synergistic factor of 3.67. The incorporation of PAA into the DBD system obviously reduced energy consumption with a 191 % increase in energy yield. The synergistic effects of PAA/DBD can be attributed to the PAA-activating factors generated by DBD (including O3, ultraviolet (UV), H2O2, and heat) and the enhanced effects of H2O2 and CH3COOH (released by PAA) on DBD. This symbiotic relationship between PAA and DBD enhanced the production of various reactive species (including •OH, 1O2, •O2−, ONOO−, and •CH3). The contributions of these reactive species to SMX removal followed the sequence of •O2− > ONOO− >1O2 > •CH3 > •OH. Increasing the PAA dosage and/or DBD discharge power enhanced the efficiencies of the reactive species. Commonly existing anions and cations in wastewater influence the SMX removal efficiency in various ways. Based on the 12 detected intermediates, probable degradation pathways for SMX were proposed. The ecotoxicity assessments of SMX and its intermediates indicated that PAA/DBD treatment minimized the negative effects of SMX on the environment. These observations demonstrated the versatility of PAA/DBD in providing a green, efficient, and innovative approach for removing antibiotics from the water environment.