A series of novel subphthalocyanine (SubPc) derivatives with bulky electron-donating substituents were synthesized for visible light-induced photocatalytic and photoelectrochemical hydrogen production. SubPc derivatives were decorated with bulky thiophenoxy (coded SubPc 1–2) and phenoxy (coded SubPc 3–4) substituents to compare the influence of the nature of the peripheral bulky substituents on the photophysical and photocatalytic activity of SubPc. The highest photocatalytic performance was obtained from SubPc 4, having diphenyl phenoxy substituents with an H2 production rate of 7.233 mmol g-1h−1. The photocatalytic hydrogen evolution activities of all SubPc sensitized TiO2 photocatalysts enhanced approximately four times in the presence of Pt co-catalyst. The photocatalysts showed remarkable long-term stability and reproducibility of H2 evolution over 24-hour irradiation. SubPc 4-based photocatalytic system reached a considerable catalytic activity with the H2 production of 16.022 mmol g−1 and a turnover number (TON) value of 34,089 for 24 h irradiation. Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TD-DFT) studies were carried out to better understand the photocatalytic abilities of SubPc derivatives and develop a symbiotic connection with experimental investigations. The results highlight the importance of peripheral substituents in modifying electron density, dipole moment, and HOMO-LUMO energy levels and improving SubPc derivative light-harvesting performance. The presence of 2,6-diisopropyl on SubPc derivatives (SubPc 2 and 4) caused a significant change in the properties, resulting in favourable electron transport characteristics and, therefore, improving photocatalytic performance. Furthermore, the incorporation of TiO2, as shown in SubPc 1@TiO2 and SubPc 2@TiO2, resulted in a modest reduction in chemical hardness, implying increased charge transfer inside the molecule and, as a consequence, enhancing its efficacy as a sensitizer. These theoretical discoveries provide a solid foundation for the customized design and optimization of SubPc derivatives for effective photocatalytic applications.