In this study, the degradation of sulfonamide antibiotics was investigated through persulfate-enhanced UV advanced oxidation process. Factors that may affect the degradation efficiency were analyzed. Results showed that the persulfate imposed a significant enhancement on the UV oxidation process during the sulfathiazole degradation. The combined process of UV/persulfate can effectively remove about 96% of sulfathiazole within 60 min. With the increase in the dosage of persulfate, the removal efficiency increased as well. Different water matrix almost had no effect on the removal efficiency. Two intermediates were found during the sulfathiazole degradation. It can be predicted that the combined process of UV/persulfate has a broad application prospect for removing sulfonamide antibiotics in water treatment.