The effects of ligand modification on the catalytic mechanism of hydrogen production by Ni(PyS)3 − derivatives, made with electron-withdrawing and -donating substitutions to the pyridinethiolate (PyS)− ligands, are studied experimentally and computationally using density functional theory. Thermodynamic data, spin density maps, and frontier molecular orbital diagrams were generated for reaction intermediates. Comparison of computed values for E0 and pKa with experimental values supports the proposed mechanisms. The rate of electrochemical hydrogen production is correlated with the effect of ligand modification. Notably, the presence of an electron-donating substituent favors an alternative mechanism for hydrogen production. Computationally it was determined that the electron-donating substituent causes deviation from the original chemical− electrochemical−chemical−electrochemical (CECE) mechanism of Ni(PyS)3 − to a CCEE mechanism, while the CECE mechanism is maintained for all catalysts substituted with electron-withdrawing groups.