Four novel polypyridine cobalt(II) complexes were developed based on a hexadentate ligand scaffold bearing either electron-withdrawing (-CF3) or electron-donating (-OCH3) groups in different positions of the ligand. Experiments and theoretical calculations were combined to perform a systematic investigation of the effect of the ligand modification on the hydrogen evolution reaction. The results indicated that the position, rather than the type of substituent, was the dominating factor in promoting catalysis. The best performances were observed upon introduction of substituents on the pyridine moiety of the hexadentate ligand, which promoted the formation of the Co(II)H intermediate via intramolecular proton transfer reactions with low activation energy. Quantum yields of 11.3 and 10.1 %, maximum turnover frequencies of 86.1 and 76.6 min(-1), and maximum turnover numbers of 5520 and 4043 were obtained, respectively, with a -OCH3 and a -CF3 substituent.