Oxygen vacancy modulation has emerged as a prevalent strategy to improve the performance of heterogeneous catalysts. By far, the impact of oxygen vacancy rearrangement on the efficiency of Fenton-like reaction remains largely unknown. In this paper, Fe-containing polyoxometalates were coupled with defect-rearranged TiO2 to construct defective Fenton-like photocatalysts. Experimental characterizations revealed that defect rearrangement facilitated the interfacial transfer of electrons from TiO2 to polyoxometalate molecules. Fenton-like photocatalysts with rearranged defects exhibited 5 and 3.5 times higher activity for the synergetic degradation of toxic dye and 5-Sulfosalicylic acid than pristine TiO2. This enhancement was ascribed to the beneficial role of oxygen vacancy modulation for activating oxygen and H2O2 molecules into O-center dot(2)- and (OH)-O-center dot radicals. Our work provides new opportunities for exploring efficient Fenton-like photocatalysts for environmental remediation.