A metal–organic framework, MIL-101(Cr), was used to adsorb sulfamethoxazole (SMZ) in water and activated persulfate (PS) oxidation was investigated to regenerate SMZ-saturated MIL-101(Cr). Adsorption and oxidation were combined in this study. MIL-101(Cr) was characterized by SEM, BET, XPS and FT-IR analyses. Effects of various operating parameters on adsorption efficiency were studied. The dosages of persulfate for SMZ desorption and oxidation were investigated. The results showed that the recommended pH was 6–8 for SMZ adsorption and optimum MIL-101(Cr) dosage was 0.1 g L⁻¹. SMZ adsorption by MIL-101(Cr) was a spontaneous process and nearly exothermic. Saturation adsorption capacity was achieved in 180 s and the adsorption followed the pseudo-second-order model. The maximum adsorption amount of MIL-101(Cr) to SMZ was 181.82 mg g⁻¹ (Langmuir). MIL-101(Cr) also showed good adsorption capacities for sulfachloropyridazine (SCP), sulfamonomethoxine (SMM), and sulfadimethoxine (SDM). Persulfate was helpful for SMZ desorption from the surface of saturated MIL-101(Cr) and sufficient persulfate could simultaneously oxidize the SMZ. XPS analysis showed that the structure of MIL-101(Cr) was stable after the persulfate oxidation process. Regenerated MIL-101(Cr) had the same level of adsorption capacity as fresh MIL-101(Cr). An adsorption–oxidation combined process may be set up based on the results. This study provides basic data for the deep treatment of organic micropollutants in urban water bodies.