A comparative study between the visible light induced photo-Fenton system (light/Fe2+/H2O2, P-F) and photo-Fenton like system (light/Fe2+/S2O82−, P-FL) was carried out for the degradation of antibiotic sulfamethazine (SMZ). It was found that white-LED light could enhance the SMZ degradation in both photochemical systems. The optimum dosage ratio of [Fe2+]:[Oxidant] was determined as 1:10 in the two systems. However, compared to the P-F system, the P-FL system would consume five times of catalyst/oxidant (i.e. 1 mM [Fe2+]/10 mM [persulfate]) amount to achieve approximately complete decomposition of SMZ within 30 min. The P-FL system could also effectively degrade SMZ at a broad pH range of 2–5 (the P-F system was 3–4). Furthermore, the present of common inorganic ions exhibited different effects on the SMZ degradation as for the two systems. Although good mineralization and detoxicity of the synthetic wastewater were observed in the two systems, identifications of the released sulfate and intermediates/product suggested different SMZ degradation pathways. Cleavage of the SN bond under hydroxyl radical (OH) attacking was dominant in the P-F system, while sulfate radical (SO4−) attacking of the amine group in the benzene ring followed by cleavage of CN bonds in the heterocyclic ring was the main SMZ degradation pathway in the P-FL system.