Enhancement of sludge dewaterability is key for sludge management and disposal of wastewater treatment plants (WWTP). In this study, the Fe2+-peroxymonosulfate (PMS) conditioning approach was first used to oxidize the primary sludge from the primary sedimentation tank of a full scale WWTP. The combination of Fe2+ (0.05-0.5 g/g TSS) and PMS (0.05-0.5 g/g TSS) could significantly improve the dewaterability of primary sludge. The optimal addition amount of Fe2+ and PMS was 0.1 g/g TSS and 0.25 g/g TSS, respectively, under which the capillary suction time (CST) and specific resistance to filtration (SRF) of the sludge was reduced by 79% and 95%. The physicochemical properties (particle size, zeta potential, EPS composition) of the primary sludge before and after oxidative conditioning were measured. Results showed that sulfate radicals generated from Fe2+-PMS system effectively reduced organic matter in different EPS fractions, further destroying sludge floc cells. Then the bound water in the sludge flocs was released, thereby improving the sludge dewaterability. The microscopic morphology also indicated that the sludge flocs have a blocky structure with tight texture before conditioning. After conditioning, the sludge flocs become smaller, and many irregular pores are formed on the surface, which facilitates the passage of internal moisture. Economic analysis showed that Fe2++PMS conditioning is more economical than the traditional Fenton method.