Alkaline hydrogen evolution reaction (HER) offers a near-zero-emission approach to advance hydrogen energy. However, the activity limited by the multiple reaction steps involving H2O molecules transfer, absorption, and activation still unqualified the thresholds of economic viability. Herein, we proposed a multisite complementary strategy that incorporates hydrophilic Mo and electrophilic V into Ni-based catalysts to divide the distinct steps on atomically dispersive sites and thus realize sequential regulation of the HER process. The Isotopic labeled in situ Raman spectroscopy describes 4-coordinated hydrogen bonded H2O to be free H2O passing the inner Helmholtz plane in the vicinity of the catalysts under the action of hydrophilic Mo sites. Furthermore, potential-dependent electrochemical impedance spectroscopy (EIS) reveals that electrophilic V sites with abundant 3d empty orbitals could activate the lone-pair electrons in the free H2O molecules to produce more protic hydrogen, and dimerize into H2 at the Ni sites. By the sequential management of reactive H2O molecules, NiMoV oxides multisite catalysts surpass Pt/C hydrogen evolution activity (49 mV@10 mA∙cm−2 over 140 h). Profoundly, this study provides a tangible model to deepen the comprehension of the catalyst–electrolyte interface and create efficient catalysts for diverse reactions.