[en] Highlights: • A strategy has been developed to change inert monolayered MoS₂ as efficient photocatalyst. • Resulted Mo-S catalyst has remarkable photocatalytic activity for organic dye degradation. • The catalyst exhibits excellent performance of photocatalytic hydrogen evolution reaction (HER). • Underlying mechanisms for the electronic structure evolution of Mo-S monolayers is revealed. Molybdenum disulfide (MoS₂) has a theoretical catalytic activity comparable to Pt but in practice is a poor catalyst in bulk form due to the scarcity of metal edge sites and low electrical conductivity. Recent developments on MoS₂ monolayers (MLs) are more encouraging in developing cheap and efficient catalysts, but the majority metal atoms are on the basal plane and catalytically inactive. The rapid recombination of the electron-hole pairs and electronic band structure of the most stable 2H-MoS₂ MLs are also unsuitable for efficient photocatalysis, especially for solar-driven water splitting. Here, we show that reducing the lateral size and creating sulphur (S) vacancies of MoS₂ MLs not only increases dramatically the density of catalytically active sites, but also adjusts the band structure to become highly suitable for solar-driven catalysis. In addition, this preparation efficiently avoids fast charge recombination associated with MoS₂, improves light harvesting, and gives a newly formed metallic state to transfer electrons for photocatalytic reactions. By way of example, we have demonstrated remarkable photocatalytic degradation of methylene blue (MB) and methylene orange (MO) dyes using the S-depleted Mo-S nanocrystals (NCs, 2–25 nm). The NCs are also promising to efficiently generate hydrogen (H₂) from water with sacrificial reagents and solar light irradiation. Our study shows how careful design and modification of materials can result in highly efficient photocatalysts, which give considerable opportunities of the transition metal dichalcogenides (TMDs) beyond just MoS₂ to develop highly efficient and economic catalysts.