Catalysts with a single atom site allow highly tuning of the activity, stability, and reactivity of heterogeneous catalysts. Therefore, atomistic understanding of the pertinent mechanism is essential to simultaneously boost the intrinsic activity, site density, electron transport, and stability. Here, we report that atomically dispersed nickel (Ni) in zincblende cadmium–zinc sulfide quantum dots (ZCS QDs) delivers an efficient and durable photocatalytic performance for water splitting under sunlight. The finely tuned Ni atoms dispersed in ZCS QDs exhibit an ultrahigh photocatalytic H2 production activity of 18.87 mmol hour−1 g−1. It could be ascribed to the favorable surface engineering to achieve highly active sites of monovalent Ni(I) and the surface heterojunctions to reinforce the carrier separation owing to the suitable energy band structures, built-in electric field, and optimized surface H2 adsorption thermodynamics. This work demonstrates a synergistic regulation of the physicochemical properties of QDs for high-efficiency photocatalytic H2 production.