Adsorption characteristics of high-silica zeolites (HSZSM-5) for two selected sulfonamide antibiotics (SAs) (sulfamethoxazole and sulfadiazine) were investigated. The SAs were almost completely (>90%) removed from the water by HSZSM-5. Adsorption followed second-order kinetics with liquid-film diffusion as the dominant mechanism. SA adsorption capacity on high-silica zeolites was examined in terms of pH, temperature, and the presence of natural organic matter (NOM). HSZSM-5 had better adsorption performance in acidic conditions, and the apparent distribution coefficient indicated that SA0 species were the major contribution to the overall adsorption at pH of 2-10. Adsorption of SAs on HSZSM-5 was a spontaneous and exothermic physisorption process. SA removal by HSZSM-5 was a mixed mechanism through ion-exchange and hydrophobic interaction. HSZSM-5 has potential application prospects in removing SAs from wastewater.