A single-atomic activation strategy on the basal planes of ZnIn₂S₄ (ZIS) nanosheets significantly enhances photocatalytic hydrogen evolution (PHE). The study reports a simple one-step hydrothermal method to prepare Mo-doped ZIS (Mo-ZIS) nanosheets as a highly active PHE catalyst. Mo substitution for In atoms in ZIS induces spatial charge redistribution, promoting charge separation and optimizing the Gibbs free energy of H* adsorption on S atoms at basal planes. Mo-ZIS exhibits a PHE rate of 6.71 mmol·g⁻¹·h⁻¹, over 10 times that of pristine ZIS, with an apparent quantum efficiency (AQE) of 38.8% at 420 nm. This study provides insights into the coordination configuration and electronic modulation from single-atomic decoration, offering mechanistic understanding for developing advanced photocatalysts via non-precious metal atomic modification. ZIS is a 2D metal sulfide photocatalyst with suitable band gap and sunlight responsivity. HER activity primarily originates from the (110) crystal plane, while the (001) basal plane shows catalytic inertness due to strong H adsorption. Introducing weakly metallic atoms onto 2D basal planes can adjust electron distribution, weakening H adsorption and optimizing Gibbs free energy. Mo, with a half-full d orbital and atomic radius close to Zn and In, is suitable for replacing these atoms to modulate ZIS electronic structures. A top-down pyrolysis/emission strategy was previously used for anchoring metal atoms, but it requires high temperatures and reductive atmospheres, unsuitable for most photosensitive semiconductors. This work reports a successful fabrication of Mo-ZIS via a one-step hydrothermal method. Mo-ZIS shows significantly enhanced charge-separation efficiency and PHE activity. Under 1 sun illumination, Mo-ZIS achieves an ultrahigh PHE rate of 6.71 mmol·g⁻¹·h⁻¹, over 10 times that of pristine ZIS. The atomic Mo substitution for In atoms mediates the electronic structure of nearby S sites on basal planes, improving charge separation and utilization efficiencies, resulting in superb PHE performance.A single-atomic activation strategy on the basal planes of ZnIn₂S₄ (ZIS) nanosheets significantly enhances photocatalytic hydrogen evolution (PHE). The study reports a simple one-step hydrothermal method to prepare Mo-doped ZIS (Mo-ZIS) nanosheets as a highly active PHE catalyst. Mo substitution for In atoms in ZIS induces spatial charge redistribution, promoting charge separation and optimizing the Gibbs free energy of H* adsorption on S atoms at basal planes. Mo-ZIS exhibits a PHE rate of 6.71 mmol·g⁻¹·h⁻¹, over 10 times that of pristine ZIS, with an apparent quantum efficiency (AQE) of 38.8% at 420 nm. This study provides insights into the coordination configuration and electronic modulation from single-atomic decoration, offering mechanistic understanding for developing advanced photocatalysts via non-precious metal atomic modification. ZIS is a 2D metal sulfide photocatalyst with suitable band gap and sunlight responsivity. HER activity primarily originates from the (110) crystal plane, while the (001) basal plane shows catalytic inertness due to strong H adsorption. Introducing weakly metallic atoms onto 2D basal planes can adjust electron distribution, weakening H adsorption and optimizing Gibbs free energy. Mo, with a half-full d orbital and atomic radius close to Zn and In, is suitable for replacing these atoms to modulate ZIS electronic structures. A top-down pyrolysis/emission strategy was previously used for anchoring metal atoms, but it requires high temperatures and reductive atmospheres, unsuitable for most photosensitive semiconductors. This work reports a successful fabrication of Mo-ZIS via a one-step hydrothermal method. Mo-ZIS shows significantly enhanced charge-separation efficiency and PHE activity. Under 1 sun illumination, Mo-ZIS achieves an ultrahigh PHE rate of 6.71 mmol·g⁻¹·h⁻¹, over 10 times that of pristine ZIS. The atomic Mo substitution for In atoms mediates the electronic structure of nearby S sites on basal planes, improving charge separation and utilization efficiencies, resulting in superb PHE performance.