Engineering defects in crystalline electrocatalysts is an effective approach to tailor the electronic structure and number of active sites, which are essential for the intrinsic activity of the hydrogen evolution reaction (HER). Unlike previously reported methods, we demonstrate a confinement effect using a mesoporous template for in situ fabrication of cationic W vacancies in as-prepared ordered mesoporous tungsten phosphide (WP) nanostructures by adjusting the nonstoichiometric ratio of the precursor elements. With a plenty of W vacancies and ordered mesoporosity, the as-prepared catalyst WP-Mesop exhibits better catalytic performance than the catalysts without mesopores and/or vacancies. The WP-Mesop shows an ultralow overpotential of 175 mV in acid and 229 mV in alkaline at 100 mA cm^–2 and stability of 48 h without structural collapse in both acid and alkaline media. Meanwhile, density functional theory calculations further reveal that the activation barrier for HER can be lowered by introducing cationic W vacancies. This strategy can be extended to generate cationic defects in other transition metal phosphides to improve their HER activities.