A 2D micron-sized MOF sheet, namely BUC-21(Fe), was synthesized hydrothermally from FeSO4·7H2O, 1,3‐dibenzyl‐2‐imidazolidone‐4,5‐dicarboxylic acid (H2L) and 4,4′‐bipyridine (bpy), which exhibited efficient removal of chloroquine phosphate (CQ) as emerging organic pollutant model via photon-Fenton process at pH = 5.0. The generated ·OH concentration was 242.5 μmol L−1 with H2O2 consumption efficiency of 83.2%. The hydroxyl radical (·OH) was the primary reactive specie at the whole process, whereas superoxide radical (·O2−) could boost the Fenton-like reaction at neutral pH. The oxidation state and content of iron in BUC-21(Fe) was detected by X-ray absorption fine structure (XAFS), in which 62% and 45% Fe2+ could be observed in the fresh sample and the used sample after photo-Fenton reaction. The CQ removal efficiency decreased from 100% to 68.3% when Fe sites were locked by phosphate, directly confirming the important role of Fe in the photo-Fenton reaction. The mechanism was proposed with the help of electrochemistry and density functional theory (DFT) calculation, which revealed that the photoinduced election was excited from oxygen atoms to Fe ions. The CQ was degraded into small molecules with low toxicity, and the degradation pathway was proposed. BUC-21(Fe) was water stable and showed excellent performance for photo-Fenton degradation of various organic contaminants (sulfamethoxazole (SMX) and bisphenol A (BPA)).