Ligand-protected gold (Au) nanoclusters (NCs) are fascinating for catalytic applications due to their unique electronic structure and catalytic activity endowed by quantum size effects. The identification of the number of ligands in NCs not only determines the catalytic behavior of their active sites, but also directly affects their stability. Therefore, establishing a physical picture including the number of ligands on the surface of NCs, geometric structure, thermodynamic stability and catalytic activity is crucial for balancing stability and catalytic performance. Combined with density functional theory calculations, the catalytic behavior of phosphine ligand-protected Au NCs (including [Au9(PPh3)8]3+, [Au10(PPhCy2)6Cl3]+, [Au11(PPh3)8Cl2]+ and [Au13(PMe2Ph)10Cl2]3+) with ligand shedding processes were systematically investigated using gas-phase CO oxidation as a probe reaction. The results show that the geometric configurations of these Au NCs evolve towards a planar structure with the shedding of ligands. Their chemical activity shows a distinct linear relationship with their d orbital centers, which are governed by the electron coupling between the surface ligands and the Au core for each ligand of Au NCs. The geometrical structure–chemical activity relationship was uncovered for these ligand Au NCs. These results provide important knowledge for precisely regulating the activity and stability of ligand-protected metal NCs for energy conversion at the atomic level.