Maneuvering the architecture and composition of semiconductors is essential to optimizing their performance in photocatalytic solar-to-fuel conversion. Here, we show that ion exchange, having a disparate mechanism with direct nucleation and growth of semiconductor crystals, can provide a new platform for rational control over the geometry and electronic structures of chalcogenide semiconductor photocatalysts. As a demonstration, the ZnSe nanocubes possessing a hollowed architecture and doped with a controllable amount of Ag+ ions are accessed via sequential ion exchange. The kinetics of the exchange reaction offers a knob for regulating the electronic structures of the Ag-doped ZnSe hollow cubes and, hence, their functions in light harvesting and photogenerated charge separation. Such synergistically geometric and optoelectronic modulation of ZnSe brings an order of magnitude enhancement in photocatalytic H2 evolution activity relative to commercial ZnSe powders. Our study corroborates that ion exchange may open up new horizons for judicious fabrication and engineering of semiconductor-based photocatalyst materials.