Prospective life-cycle assessment was applied to a hypothetical large-scale (1 gigawatt (GW) annual average) photo-electrochemical (PEC) plant producing hydrogen (H2) from splitting water. The approach provides early insight into key variables driving the net energy balance, and suggests directions for future research. The life-cycle approach spans raw material extraction, processing, manufacturing, deployment, operations and decommissioning of a technology. We focused on three indices of net energy performance: life-cycle primary energy balance, energy return on energy invested, and energy payback time, and investigate the net energy significance of six characteristics describing the PEC life cycle: (1) embodied energy (the embodied energy of a system element is the cumulative energy input required to produce it in finished form from raw starting materials) of active cell materials, (2) embodied energy of inactive module materials, (3) energy intensity of active cell fabrication, (4) energy intensity of PEC module assembly, (5) initial energy use for production of balance of system (BOS), and (6) ongoing energy use for operation and end-of-life of BOS. We develop and apply a system model describing material and energy flows during the full life-cycle of louvered thin-film PEC cells and their associated modules and BOS components. We find that fabrication processes for the PEC cells are important drivers of net energy performance: the energy intensity of the thin-film deposition of active cell materials strongly affects the overall net energy. We confirm that solar-to-H2 (STH) conversion efficiency and cell life span are key focus areas for improving net energy performance of a PEC H2 system. We discuss these and other system parameters, and highlight pathways to improve net energy performance.