Introducing crystal defects into iron based metal-organic frameworks (Fe-MOFs) is regarded as a promising strategy to enhance Fenton-like performance. However, developing a facile and effective strategy to construct defective Fe-MOFs as highly efficient Fenton-like catalyst is still a challenge. Herein, MIL-100(Fe) (Def-MIL-100(Fe)) with missing ligands defects was synthesized by a simple heterogeneous reaction using zero-valent iron. The bisphenol A degradation efficiency in the Def-MIL-100(Fe)/H2O2 system reached up to 91.26% within 10min at pH 4 with a low catalyst dosage of 0.05g/L, while the perfect MIL-100(Fe) has almost no Fenton-like performance. It was observed that missing ligands defects in the Def-MIL-100(Fe) play a key role in the Fenton-like reaction. The missing ligands defects could increase the Lewis acidity for fast H2O2 adsorption and accelerate the electron transfer between FeII and FeIII cycling, leading to faster and more·OH generation. Moreover, the missing ligands defects could promote the mass transfer for improving·OH utilization efficiency. This work provides a novel strategy to construct defective Fe-MOFs as highly efficient Fenton-like catalyst to degrade organic pollutants in water.