In this study, sulfide-modified nanoscale zero-valent iron (S-nZVI) was employed to activate persulfate (PS) and hydrogen peroxide (H2O2) for the removal of sulfamethazine (SMT). The potential influencing factors, such as oxidant concentration, SMT concentration, Fe/S molar ratio and initial pH, were examined. The removal of SMT in the S-nZVI/PS system increased with the increasing PS concentration, while there was an optimum H2O2 concentration in the S-nZVI/H2O2 system. The S-nZVI/H2O2 system showed much stronger oxidative capacity than the S-nZVI/PS system under the same fitting condition. Moreover, the S-nZVI/PS system was more susceptible to the molar ratio of Fe/S in S-nZVI, and a higher SMT removal was achieved under conditions of Fe/S >= 40. Nevertheless, the S-nZVI/PS system was efficient over a wide pH range of 3-9, while the efficient pH in the S-nZVI/H2O2 system was confined to just 3. In addition, the SMT removal by the S-nZVI/PS system was further examined in simulated groundwater and it was found that the influence of groundwater components on the removal of SMT was insignificant over the pH range of 5-8, but a notable negative effect was observed at pH 9.