The structure−property relationship considering isomerism-tuned photoluminescence and efficient catalytic activity of silver nanoclusters (NCs) is exclusive. Asymmetrical dithiophosphonate NH 4 [S 2 P(OR)(p-C 6 H 4 OCH 3 )] ligated first atomically precise silver NCs [Ag 21 {S 2 P(OR)(p-C 6 H 4 OCH 3 )} 12 ]PF 6{where, R = n Pr (1), Et (2)} were established by single-crystal X-ray diffraction and characterized by electrospray ionization mass spectrometry, NMR ( 31 P, 1 H, 2 H), X-ray photoelectron spectroscopy, UV−visible, energy-dispersive X-ray spectroscopy, Fourier transforms infrared, thermogravimetric analysis, etc. NCs 1 and 2 consist of eight silver atoms in a cubic framework and enclose an Ag@Ag 12 -centered icosahedron to constitute an Ag 21 core of T h symmetry, which is concentrically inscribed within the S 24 snubcube, P 12 cuboctahedron, and the O 12 truncated tetrahedron formed by 12 dithiophosphonate ligands. These NCs facilitate to be an eight-electron superatom (1S 2 1P 6 ), in which eight capping Ag atoms exhibit structural isomerism with documented isoelectronic [Ag 21 {S 2 P(O i Pr) 2 } 12 ]PF 6, 3. In contrast to 3, the stapling of dithiophosphonates in 1 and 2 triggered bluish emission within the 400 to 500 nm region at room temperature. The density functional theory study rationalized isomerization and optical properties of 1, 2, and 3. Both (1, and 2) clusters catalyzed a decarboxylative acylarylation reaction for rapid oxindole synthesis in 99% yield under ambient conditions and proposed a multistep reaction pathway. Ultimately, this study links nanostructures to their physical and catalytic properties.