Abstract Density functional theory (DFT) calculations are carried out to investigate the structural and electronic properties of a series of hexanuclear vanadium oxide clusters V6On−/0 (n=12–15). Generalized Koopmans’ theorem is applied to predict the vertical detachment energies (VDEs) and simulate the photoelectron spectra (PES) for V6On− (n=12–15) clusters. Extensive DFT calculations are performed in search of the lowest-energy structures for both the anions and neutrals. All of these clusters appear to prefer the polyhedral cage structures, in contrast to the planar star-like structures observed in prior model surface studies for the V6O12 cluster. Molecular orbitals are performed to analyze the chemical bonding in the hexanuclear vanadium oxide clusters and provide insights into the sequential oxidation of V6On− (n=12–15) clusters. The V6On− (n=12–15) clusters possess well-defined V5+ and V3+ sites, and may serve as molecular models for surface defects. Electron spin density analyses show that the unpaired electrons in V6On− (n=12–14) clusters are primarily localized on the V3+ sites rather than on the V5+ sites. The difference gas phase versus model surface structures of V6O12 hints the critical roles of cluster–substrate interactions in stabilizing the planar V6O12 cluster on model surfaces.