Display omitted •Peroxymonosulfate and electrolysis have synergistic effect on the degradation of CECs.•The mechanism of electrochemically activated peroxymonosulfate is proposed.•A prediction model on the effect of water matrices on SMX removal is built using RSM.•Electrochemically activated peroxymonosulfate has great potential for application. Electrochemically activated persulfate is an emerging advanced oxidation process for the removal of contaminants of emerging concern (CECs). The degradation of CECs, including carbamazepine (CBZ), bisphenol S (BPS), propranolol (PPL) and sulfamethoxazole (SMX) using electrochemically activated peroxymonosulfate (EA-PMS) was systematically investigated in this work. Over 80% of all the forementioned CECs were removed within 30 min. It exhibited a good synergistic effect between PMS and electrolysis on the degradation of CECs. The results of linear sweep voltammetry (LSV) indicated that a transition structure between BDD anode and PMS (BDD (PMS)*) was likely responsible for the synergistic effect. Hydroxyl radical (HO·) and sulfate radical (SO4·−) were proved to be the primary reactive species, of which HO· played the leading role. The increase of current density and PMS dosage accelerated the degradation of SMX, while initial pH from 3.0 to 11.0 had a limited effect on the degradation of SMX. Moreover, the influences of common ions and natural organic matter (NOM) on the degradation of SMX were comprehensively assessed using response surface methodology (RSM), and a prediction model was built via RSM. The performance of EA-PMS on the degradation of SMX in actual water was even better than that in pure water in this study. EA-PMS can serve as a novel and promising technology for the degradation of CECs and has great potential in practical application.