The recent thioxanthone-sensitizer-catalyzed intermolecular [2 + 2] cycloaddition induced by visible-light irradiation set the stage for the future development of feasible photo-cycloadditions. Nonetheless, the mechanism of this reaction still remains under debate, especially on the activation mode of the thioxanthone photosensitizer (energy transfer, bielectron exchange, and hydrogen transfer are all possible mechanisms). To settle this issue, systematic density functional theory calculations have been carried out. The results indicate that the energy-transfer pathway is more favorable than the bielectron-exchange and the hydrogen-transfer pathways. Meanwhile, the overall transformations involve the complexation and excitation of photosensitizer, the first C-C bond formation, the dissociation of the sensitizer, the triplet-to-singlet electronic state crossing, and the second C-C bond formation. The first C-C bond formation is the rate- and selectivity-determining step, and synergistic energy and electron transfer from photosensitizer to substrate moieties takes place along this process. On this basis, the effect of olefin substrates (ethyl vinyl ketone vs vinyl acetate) on the stereoselectivity was finally analyzed.