A general strategy, using mixed ligands, is utilized to synthesize atomically precise, intrinsically chiral nanocluster [Ag-78(DPPP)6(()SR)(42)] (Ag-78) where DPPP is the achiral 1,3-bis(diphenyphosphino)propane and SR = SPhCF3. Ag-78 crystallizes as racemates in a centric space group. Using chiral diphosphines BDPP = 2,4-bis-(diphenylphosphino)pentane, the enantiomeric pair [Ag-78(R/S-BDPP)(6)(SR)(42)] can be prepared with 100% optical purity. The chiral diphosphines gives rise to, separately, two asymmetric surface coordination motifs composed of tetrahedral R3PAg(SR)(3) moieties. The flexible nature of C-C-C angles between the two phosphorus atoms restricts the relative orientation of the tetrahedral R3PAg(SR)(3) moieties, thereby resulting in the enantiomeric selection of the intrinsic chiral metal core. This proof-of-concept strategy raises the prospect of enantioselectively synthesizing optically pure, atomically precise chiral noble metal nanoclusters for specific applications.