It is difficult to remove heavy metal-organic complexes from water by chemical precipitation because of the strong complexation ability between heavy metal ions and organics. In this study, the removal of the Cu-ethylenediaminetetraacetic acid (Cu-EDTA) complex using autocatalytic persulfate (PS) oxidation was investigated. The Cu-EDTA removal efficiency reached up to 96.57% after 90 min of treatment by PS oxidation. A higher PS concentration favored Cu-EDTA removal; An increase in the initial concentration of Cu-EDTA benefited PS activation, and a greater removal performance was obtained at a lower Cu-EDTA initial concentration (0.1 mmol L −1 ). Excessive Cu 2+ accelerated Cu-EDTA removal, while superfluous EDTA suppressed it. Relatively lower initial solution pH value favored Cu-EDTA removal. SO 4 •- , •OH, and 1 O 2 displayed significant roles in the Cu-EDTA removal process, as they destroyed the chelating sites of the Cu(II) and EDTA molecules; finally small molecular organic acids, alcohols, and NO 3 − were produced. The released Cu(II) existed in the precipitates in the forms of Cu-based carbonates, Cu-based hydroxides, and copper oxide. A possible decomposition pathway of Cu-EDTA was proposed. Overall, multipathway activation of PS induced by heavy metal complexes could be an effective technique for the removal of the heavy metal complexes. • Cu-EDTA removal is studied by PS oxidation via Cu species activation. • 1 O 2 , .•OH, and SO 4 •- contribute to Cu-EDTA decomposition. • PS activation by Cu species is mainly through Cu(I) conversion. • Possible pathways of Cu-EDTA decomposition are proposed.