In order to avoid the disadvantages of the Fenton process in wastewater treatment and reduce the cost of wastewater treatment, a series of MIL-101(Fe)-X (X = -OH, -NH2, -NO2, -H) solid Fenton catalysts were successfully prepared. The performance of these Fenton-like catalysts was studied with the Fenton experiment as a reference and methylene blue (MB) as an organic pollutant. The effects of the H2O2 concentration, catalyst dosage, and reaction pH on catalytic performance were systematically studied. The research had shown that the optimal concentration of H2O2 for catalytic reactions was 0.10 mmol/L and the pH was 3. At this point, their catalytic degradation MB performance was superior to the Fenton reaction and photocatalytic reaction. When the H2O2 participated in the reaction, the performance of MIL-101(Fe)-X (X = -OH, -NH2, -NO2, -H) in catalyzing the degradation of MB followed the rule of -OH > -NH2 > -NO2 > -H. This was due to the synergistic effect of Fenton-like catalysis and photocatalytic degradation in the catalytic degradation of MB. In addition, the electron paramagnetic resonance and electrospray ionization mass spectrometry showed that the hydroxyl radical (·OH) generated during the catalytic process first underwent a redox reaction with the highly electronegative functional groups in the MB molecule, and finally oxidized it to CO2 and H2O. This study successfully prepared commercially applicable Fenton-like catalysts and explored their optimal reaction conditions. This provides a technical reference for wastewater treatment.