N-doped single-atom Fe in graphene (Fe–N4–C) is known to have excellent electrocatalytic activity for oxygen reduction reactions (ORRs); however, it still has lower activity than Pt-based electrocatalyst. Here the ORR catalytic performance of Fe–N4–C is investigated at the quantum level. Increasing the number of N atoms, by replacing C, near the Fe-N4 moiety, increases the ORR activity. The substitution of C with N causes a local redistribution of charge, and if near to the Fe atom, this induces charge modification of the Fe atom; specifically, electrons transfer from the dxz and dyz orbitals to the dz2 orbital. Due to its geometry, the change in the dz2 orbital occupation directly impacts the bonding interaction between Fe and oxygen-containing intermediates, thus impacting the ORR catalytic performance. The use of the Fe dz2 occupancy as a reliable indicator of catalytic performance is demonstrated and potential improvements to the activity are computed.Graphical Abstract: We demonstrate that the Fe dz2 occupancy as a reliable indicator of catalytic performance and can be used to predict the activity of N-doped Fe-N4 single atom electrocatalytic moieties. We predict single atom electrocatalysts with potentials equivalent to that of Pt.