Photocatalytic water splitting to produce hydrogen using solar energy is a particularly attractive solution to increasing energy demands. However, to be of practical use, semiconductor electrodes need to be made of inexpensive, abundant elements and have a high, yet stable, photocatalytic H₂-production activity. Here we report the first demonstration of 3D mesoporous networks of Cu₂O and TiO₂ nanoparticles as highly efficient photocatalysts for hydrogen generation from water. These assembled structures feature a highly accessible pore surface that exposes a large fraction of anatase TiO₂ and Cu₂O nanoparticles to electrolytes, and has a small grain size of the constituent nanocrystals, which lead to excellent activity for H₂ evolution via a UV-visible light-driven reduction of protons. Catalytic results associated with optical UV-vis/NIR absorption and photoluminescence (PL) data indicated that the large separation of photogenerated electrons and holes at the Cu₂O–TiO₂ p–n junctions was the main reason attributed to the improved photochemical performance. Consequently, the mesoporous Cu₂O/TiO₂ catalyst containing ∼1.5 wt% Cu reaches an average H₂ evolution rate of ∼542 μmol h⁻¹ (or ∼36 133 μmol h⁻¹ g⁻¹) with an apparent quantum efficiency (QE) of 13.5% at 365 nm and an incident photon conversion efficiency of ∼4.1% under UV-visible light illumination (360–780 nm), which is one of the best HER activities among TiO₂-based semiconductor systems reported to date.