Carbon-based, non-noble metal catalysts for the oxygen reduction reaction (ORR) are crucial for the large-scale application of metal-air batteries and fuel cells. Density functional theory calculations were performed to explore the potential of atomically dispersed MN4/C (M = Fe or Mn) as an ORR catalyst in an acidic electrolyte and the ORR mechanism on MN4/C was systematically studied. The results indicated MN4 as the active site of MN4/C and a four-electron OOH transformation pathway as the preferred ORR mechanism on the MN4/C surface. The Gibbs free energy diagram showed that the rate-determining step of the FeN4/C and MnN4/C catalysts is the formation of the second H2O molecule and OOH*, respectively. FeN4/C exhibited higher thermodynamic limiting potential (0.79 V) and, thus, higher ORR activity than MnN4/C (0.52 V) in an acidic environment; its excellent catalytic performance is due to the nice electron structure and adsorption properties of the FeN4 site. Therefore, this work demonstrates that atomically dispersed MN4/C is a promising catalyst for the ORR.