The viewpoints on whether high concentration of chloride ion (Cl−) promote or inhibit the oxidation activity of activated persulfates are still inconclusive. Furthermore, the degradation of organic pollutants by the persulfates in the presence of high Cl− concentrations without any activation medium has not yet been studied. In this work, the efficiency and mechanism of degradation of organic pollutants such as carbamazepine (CBZ), sulfadiazine (SDZ) and phenol (PN) by Cl− activated PMS (denoted as Cl−/PMS) were investigated. Results showed that Cl− could effectively activate PMS for complete removal of CBZ, SDZ and PN with reaction kinetic constants of 0.4516 min− 1, 0.01753 min− 1 and 0.06805 min− 1, respectively. Parameters such as PMS dose, Cl− concentration, solution pH, and initial concentrations of organic pollutants that affecting the degradation efficiencies of the Cl−/PMS process were optimized. Unlike conventional activated persulfates, it was confirmed that the free chlorine was the main active species in the Cl−/PMS process. Finally, the degradation by-products of CBZ and SDZ as well as their toxicity were detected, and a possible degradation pathway for CBZ and SDZ were proposed. Though higher toxic chlorinated by-products were generated, the Cl−/PMS process was still an efficient oxidation method for the removal of organic pollutants in aqueous solutions which contains high concentration of Cl−.