During the last several decades TiO2 photocatalytic oxidation using the molecular oxygen in air has emerged as a promising method for the degradation of recalcitrant organic pollutants and selective transformations of valuable organic chemicals. Despite extensive studies, the mechanisms of these photocatalytic reactions are still poorly understood due to their complexity. In this review, we will highlight how the oxygen-18 isotope labeling technique can be a powerful tool to elucidate complicated photocatalytic mechanisms taking place on the TiO2 surface. To this end, the application of the oxygen-18 isotopic-labeling method to three representative photocatalytic reactions is discussed: (1) the photocatalytic hydroxylation of aromatics; (2) oxidative cleavage of aryl rings on the TiO2 surface; and (3) photocatalytic decarboxylation of saturated carboxylic acids. The results show that the oxygen atoms of molecular oxygen can incorporate into the corresponding products in aqueous solution in all three of these reactions, but the detailed incorporation pathways are completely different in each case. For the hydroxylation process, the O atom in O2 is shown to be incorporated through activation of O2 by conduction band electrons. In the cleavage of aryl rings, O atoms are inserted into the aryl ring through the site-dependent coordination of reactants on the TiO2 surface. A new pathway for the decarboxylation of saturated carboxylic acids with pyruvic acid as an intermediate is identified, and the O2 is incorporated into the products through the further oxidation of pyruvic acid by active species from the activation of O2 by conduction band electrons.