In this work, we use physically realistic kinetics models of photo-driven water oxidation on TiO2 to evaluate how hole generation, bulk diffusion, surface mobility and reaction are coupled. The calculations show that hole formation and diffusion in the bulk crystal dominate O2 formation at low light intensity, resulting in an apparent high order dependence of the O2 production rate on holes. As light intensity increases, the water splitting reaction becomes nearly independent of hole concentrations because of a buildup of intermediates that can only react thermally. Although it is believed that high hole mobility is a requirement for hole accumulation, a comparison of predicted to observed surface species indicates that immobilized holes dominate surface reactivity. The primary surface reaction sites are predicted to involve oxygen atoms that bridge two Ti atoms, supplied with OH formed by water dissociation on Ti sites. Because of the similarity among photocatalytic water oxidation mechanisms on diverse metal oxide semiconductors, which have generally low hole mobilities, the findings from this work may be relevant to them as well. If so, manipulations of hole mobility and accelerating the rate of thermal steps may provide a general pathway for improving water oxidation efficiency.