Sulfonamide antibiotics in water have potential threat to environments. In this context, MIL-101(Cr) (Materials Institute Lavoisier-101(Cr)) was applied to adsorb sulfadimethoxine (SDM), sulfamonomethoxine (SMM), and sulfachloropyridazine (SCP) in water and persulfate was chosen to degrade the sulfonamides adsorbed by MIL-101(Cr). A recommended dosage was 0.15 g/L for sulfonamides adsorption. In pH 5–7, the adsorption capacity of MIL-101(Cr) to three sulfonamides reached the maximum and decreased with increasing salt concentrations. Sulfonamides adsorption followed the pseudo-second-order kinetic model. The total adsorption amount was 340.90 mg/g when MIL-101(Cr) simultaneously adsorbed all three sulfonamides at 100 mg/L. Electrostatic interaction and hydrogen bonding were the main mechanisms for three sulfonamides adsorption on MIL-101(Cr). SDM, on the surface of MIL-101(Cr), was effectively oxidized at 60 °C by persulfate. The adsorption capacity of MIL-101(Cr) decreased with the increase of oxidation times. Persulfate could be used to regenerate saturated adsorbents to construct an adsorption-oxidation process. This provides a reference for deeply treatment of organic micro-pollutants in water.