It is still a challenge to construct single‐atom level reduction and oxidation sites in single‐component photocatalyst by manipulating coordination configuration for photocatalytic water splitting. Herein, the atomically dispersed asymmetric configuration of six‐coordinated Co‐S2O4 (two exposed S atoms, two OH groups, and two Co─O─Zn bonds) suspending on ZnIn2S4 nanosheets verified by combining experimental analysis with theoretical calculation, is applied into photocatalytic water splitting. The Co‐S2O4 site immobilized by Vs acts as oxidation sites to guide electrons transferring to neighboring independent S atom, achieving efficient separation of reduction and oxidation sites. It is worth mentioning that stabilized Co‐S2O4 configuration show dynamic structure evolution to highly active Co‐S1O4 configuration (one exposed S atom, one OH group, and three Co─O─Zn bonds) in reaction, which lowers energy barrier of transition state for H2O activization. Ultimately, the optimized photocatalyst exhibits excellent photocatalytic activity for water splitting (H2: 80.13 µmol g−1 h−1, O2: 37.81 µmol g−1 h−1) and outstanding stability than that of multicomponent photocatalysts due to dynamic and reversible evolution between stable Co‐S2O4 configuration and active Co‐S1O4 configuration. This work demonstrates new cognitions on immobilized strategy through vacancy inducing, manipulating coordination configuration, and dynamic evolution mechanism of single‐atom level catalytic site in photocatalytic water splitting.