A novel Fenton-like catalyst, metal organic framework MIL-100(Fe) with Fe-II/Fe-III mixed-valence coordinatively unsaturated iron center (CUS-MIL-100(Fe)), was synthesized, characterized, and used for the degradation of sulfamethazine (SMT). The catalytic performance of CUS-MIL-100(Fe) was investigated on the basis of various parameters, including initial pH, H2O2 concentration, catalyst dosage, and initial SMT concentration. The results showed that CUS-MIL-100(Fe) could effectively degrade SMT, with almost 100% removal efficiency within 180 min (52.4% mineralization efficiency), under the reaction conditions of pH 4.0, 20 mg L-1 SMT, 6 mM H2O2 , and 0.5 g L-1 catalyst. Moreover, CUS-MIL-100(Fe) displayed a higher catalytic activity than that of MIL-100(Fe) for SMT degradation. Combined with the physical chemical characterization, the enhanced catalytic activity can be ascribed to the incorporation of Fe-II and Fe-III CUSs (coordinatively unsaturated metal sites), the large specific surface area, as well as the formation of mesopores. Furthermore, CUS-MIL-100(Fe) exhibited a good stability and reusability. The possible catalytic mechanism of CUS-MIL-100(Fe) was tentatively proposed.