The Maillard reaction is one of the nonenzymatic post-translational modifications of proteins. Products of this reaction are considered to be related to aging diseases and the sensation of taste. In the initial stage of the Maillard reaction, Schiff base formation first occurs by the nucleophilic attack of amine nitrogen in proteins, and then, the reaction proceeds through the formation of 1,2-eminal and Amadori compounds. In this study, we computationally investigated the reaction pathway of Schiff base formation from hexoses. The optimized geometries of energy minima and transition states were calculated by using the density functional theory with the CAM-B3LYP/6-311+G(2d,2p) level of theory. The Schiff base formation progressed through three steps: two steps of carbinolamine formation and one step of dehydration. The dehydration is considered to be the rate-determining step in all hexoses because the activation barrier of the dehydration was higher than that of the carbinolamine formation. Furthermore, the steric configuration of the OH group at positions 2 and 3 affected the activation barrier.