Nitrogen-doped carbon materials featuring atomically dispersed metal cations (M–N–C) are an emerging family of materials with potential applications for electrocatalysis. The electrocatalytic activity of M–N–C materials toward four-electron oxygen reduction reaction (ORR) to H2O is a mainstream line of research for replacing platinum-group-metal-based catalysts at the cathode of fuel cells. However, fundamental and practical aspects of their electrocatalytic activity toward two-electron ORR to H2O2, a future green “dream” process for chemical industry, remain poorly understood. Here we combined computational and experimental efforts to uncover the trends in electrochemical H2O2 production over a series of M–N–C materials (M = Mn, Fe, Co, Ni, and Cu) exclusively comprising atomically dispersed M–N x sites from molecular first-principles to bench-scale electrolyzers operating at industrial current density. We investigated the effect of the nature of a 3d metal within a series of M–N–C catalysts on the electrocatalytic activity/selectivity for ORR (H2O2 and H2O products) and H2O2 reduction reaction (H2O2RR). Co–N–C catalyst was uncovered with outstanding H2O2 productivity considering its high ORR activity, highest H2O2 selectivity, and lowest H2O2RR activity. The activity–selectivity trend over M–N–C materials was further analyzed by density functional theory, providing molecular-scale understandings of experimental volcano trends for four- and two-electron ORR. The predicted binding energy of HO* intermediate over Co–N–C catalyst is located near the top of the volcano accounting for favorable two-electron ORR. The industrial H2O2 productivity over Co–N–C catalyst was demonstrated in a microflow cell, exhibiting an unprecedented production rate of more than 4 mol peroxide gcatalyst –1 h–1 at a current density of 50 mA cm–2.