Nitrogen-doped graphitic carbon materials have been extensively studied as potential replacements for Pt-based electrocatalysts for the oxygen reduction reaction (ORR). However, little is known about the catalytic mechanisms, including the parameters that determine the selectivity of the reaction. By comparing theoretical calculations of the ORR selectivity at a well-defined graphene nanostructure with experimental results, we propose a model based on interfacial solvation to explain the observed preference for the four-electron pathway in alkaline electrolytes. The hydrophobic environment around the active sites, as in enzymatic catalysis, restricts the access of water and destabilizes small ionic species such as peroxide, the product of the two-electron pathway. This model, when applied to acidic electrolytes, shows the ORR preferring the two-electron pathway, consistent with the well-known pH-dependent ORR selectivity catalyzed by graphitic carbon materials. Because of the similarity between more complex N-doped graphitic carbon materials and our model system, we can extend this model to the former and rationalize nearly all of the previously reported experimental results on the selectivity of ORR catalyzed by these materials.