The shape of a catalyst plays an important role in any catalytic reaction. The shape-dependent catalytic activities of two platinum nanoclusters (NCs) with cuboctahedral (Pt79) and octahedral (Pt85) shapes have been investigated toward oxygen reduction reaction (ORR). The energetic stability, thermal stability and dissolution limit of the NCs were investigated for their synthesis and practical usage. The four-electron (H2O formation) vs. two-electron (H2O2 formation) ORR mechanisms are systematically studied on the (111) facet of the NCs to gain more insight into the shape-dependent ORR activity and product selectivity (H2O vs. H2O2). Thermodynamic (reaction free energies) and kinetic (free energy barriers and temperature-dependent reaction rates) parameters are investigated to find out the most favored ORR pathway and product selectivity. The NC-based Pt catalysts are very efficient and selective with respect to the previously reported bulk metal (Pt, Pd, and Ag) based catalysts. Our results show that the rate-determining step is no longer a rate-determining step when the reaction is catalyzed by the cuboctahedral NC. The excellent catalytic activity of the cuboctahedral NC is attributed to the surface energy, compressive strain and d-band center position of the catalyst. Our results are very much consistent with experimental findings, and thereby such NC-based electrodes may serve as good candidates for fuel cell applications. © The Royal Society of Chemistry 2016.