The mutually corroborated electrochemical measurements and density functional theory (DFT) calculations were used to uncover the origin of electrocatalytic activity of graphene-based electrocatalysts for oxygen reduction reaction (ORR). A series of graphenes doped with nonmetal elements was designed and synthesized, and their ORR performance was evaluated in terms of four electrochemical descriptors: exchange current density, on-set potential, reaction pathway selectivity and kinetic current density. It is shown that these descriptors are in good agreement with DFT calculations, allowing derivation of a volcano plot between the ORR activity and the adsorption free energy of intermediates on metal-free materials, similarly as in the case of metallic catalysts. The molecular orbital concept was used to justify this volcano plot, and to theoretically predict the ORR performance of an ideal graphene-based catalyst, the ORR activity of which is comparable to the state-of-the-art Pt catalyst. Moreover, this study may stimulate the development of metal-free electrocatalysts for other key energy conversion processes including hydrogen evolution and oxygen evolution reactions and largely expand the spectrum of catalysts for energy-related electrocatalysis reactions.