Developing efficient photocatalysts for H2 production holds great promise to enhance solar energy conversion. In this study, we present a facile strategy to enhance H2 production by simultaneously engineering Pt cocatalyst and oxygen vacancies (Vo) on mesoporous N doping TiO2, thereby developing efficient photocatalysts for solar energy conversion. Firstly, we employed a structure-directing agent-assisted approach to synthesize a series of mesoporous N doping TiO2 spheres, inducing Vo. Among the samples, the ammonium hydroxide-assisted variant (A-TiO2) exhibited the largest specific surface area of 52.9 m2 g−1 and Vo formation. Subsequently, the Vo-containing mesoporous N-TiO2 spheres (A-TiO2), when doped with 1 wt% Pt and employing methanol as a sacrificial agent, demonstrated remarkable performance. Under simulated sunlight irradiation, A-TiO2/Pt spheres exhibited an impressive hydrogen evolution rate of 14320.89 μmol g−1 h−1, surpassing the most of previously reported TiO2 nanostructures. Experimental studies have elucidated the synergistic effect of Pt nanoparticles and Vo on TiO2 in boosting the photocatalytic reaction. This offers a facile and scalable method for the synthesis of defective TiO2 photocatalysts, thus facilitating mass production and promoting their potential commercialization.