AbstractAs an emerging class of promising porous materials, the development of two‐dimensional conductive metal organic frameworks (2D c‐MOFs) is hampered by the few categories and tedious synthesis of the specific ligands. Herein, we developed a nonplanar hexahydroxyl‐functionalized Salphen ligand (6OH‐Salphen) through a facile two‐step synthesis, which was further applied to construct layered 2D c‐MOFs through in situ one pot synthesis based on the synergistic metal binding effect of the N2O2 pocket of Salphen. Interestingly, the C2v‐symmetry of ligand endows Cu‐Salphen‐MOF with periodically heterogeneous pore structures. Benefitting from the higher metal density and shorter in‐plane metal‐metal distance, Cu‐Salphen‐MOF showcased excellent NO2 sensing performance with good sensitivity, selectivity and reversibility. The current work opens up a new avenue to construct 2D c‐MOF directly from nonplanar ligands, which greatly simplifies the synthesis and provides new possibilities for preparing different topological 2D c‐MOF based functional materials.