Notably, previous studies on defect engineering in Zr-MOFs have primarily attributed the defects to missing linkers or clusters, overlooking the role of intrinsic structural changes within the clusters themselves. Our findings challenge this view, revealing that O-vacancies in the octahedral faces of typical {Zr 6 } clusters, achieved via the removal of bridging µ 3 -OH groups during RHT, irreversibly generate coordinatively unsaturated ZrO 7 sites (Zr cus ), which cause significant structural rearrangements in the {Zr 6 } cluster. Importantly, the formation of Zr cus site in DUT-67 via dehydration nearly doubles the catalytic activity in the conversion of glyoxal to glycolic acid. DFT calculations showed that Zr cus sites significantly enhance the glyoxal binding energy to the cluster, and Zr cus sites, in combination with missing linker defects, can promote the formation of key reaction intermediates. Thus, this work not only introduces a novel approach to defect engineering in Zr-MOFs, it also emphasizes, for the first time, the synergy between missing linker defects and Zr cus sites as the key drivers of catalytic improvement. We hope these findings not only advance our understanding of MOF catalysts but will also help pave the way for developing better-performing catalytic materials in the future.