Display omitted •The Electro-Fenton and persulfate were combined to degrade metronidazole.•The CoFe2O4-PTFE electrode was used in parallel with the acetylene black-PTFE electrode.•The removal rate of metronidazole reached 90.6% by ABP/CFOP/PS system after 120 min.•The catalyst exhibited good stability and recyclability for five consecutive cycles.•The intermediates and possible degradation pathways of metronidazole were provided. A composite electrochemical oxidation system combined with Electro-Fenton and persulfate (PS) was proposed to degrade metronidazole. The CoFe2O4-PTFE (CFOP) electrode was used in parallel with the acetylene black-PTFE electrode (ABP) as the dual-cathode of Electro-Fenton. Then the Electro-Fenton was coupled with PS to degrade metronidazole in wastewater synergistically. The self-produce of H2O2, in-situ circulation of Co(II)/Co(III) and Fe(III)/Fe(II), and activation of persulfate were simultaneously conducted. After 120 min, the removal rate of metronidazole reached 90.6% by ABP/CFOP/PS system. The influence of operation parameters (dosage of PS, initial pH, current density, temperature) on the removal of metronidazole was analyzed. The catalyst exhibited good stability and recyclability for five consecutive cycles. The radical quenching and EPR tests reveal that both OH and SO4−· are identified responsible for the degradation of metronidazole. The possible decomposition pathway of metronidazole was proposed by HPLC-MS analysis. The toxicity analysis indicates that heterogeneous Electro-Fenton could reduce the toxicity of metronidazole.