An electrogenerated peroxone process was innovatively structured to effectively degrade the antiphlogistic ibuprofen (IBU) representing typical refractory pharmaceutical. The process involved electrogenerated O3 from H2O oxidation using a Ti mesh/SnO2-F anode in membrane electrode assembly (MEA) and electrogenerated H2O2 from O2 reduction using a carbon-polytetrafluoroethylene (C/PTFE) cathode. The synergetic system of H2O2 and O3 formed in situ could generate hydroxyl radical (OH) to achieve IBU degradation and total organic carbon (TOC) removal. The effects of current density, aqueous initial pH, and coexisting anions on IBU removal efficiencies were investigated and then optimized as 30 mA/cm2 and neutral condition. As a result, IBU decomposition and TOC mineralization could be finished after 10 min and 120 min electrolysis, respectively. The stability of the synergetic system combining MEA with C/PTFE-O2 was also evaluated and confirmed through multiple cycles of electrogenerated peroxone based on TOC removal efficiency. In addition, IBU degradation pathways were proposed according to the identification of intermediates (e.g. hydroxylated IBU, phenolics, and carboxylic acids) by HPLC-MS/MS. These results manifested that this synergetic system is a promising technology to remove aqueous recalcitrant pharmaceuticals.