In search of structure–activity relationships for polyoxometalate (POM)-based water reduction catalysts, nickel-monosubstituted Keggin-type POMs ([Ni(H₂O)XW₁₁O₃₉]ⁿ⁻; XP, Si, Ge) were compared with respect to their activity in photochemical hydrogen evolution. The title compound series was characterized by single-crystal X-ray diffraction methods and a wide range of spectroscopic and electrochemical techniques. Nickel substitution was identified as a crucial feature for catalytic activity through comparison with nickel-free reference POMs. Furthermore, turnover number (TON) and turnover frequency strongly depended on the heteroatom X, and the highest TON among the series was recorded for [Ni(H₂O)GeW₁₁O₃₉]⁶⁻. Photochemical hydrogen evolution activity was compared with redox and onset potentials obtained from electrochemical analyses. Furthermore, activity trends were correlated with electronic structure properties derived from density functional theory calculations.