The development of dimensionally stable anodes (DSAs) has made the chlorine evolution reaction (CER) the most important industrial anode reaction since the 1960s. However, the preparation of DSA depends on the extensive use of precious metals, Ru and Ir, which are expensive and scarce. Herein, a cationic defect adsorption–oxidation anchoring strategy to immobilize oxidized sub‐nano ruthenium clusters on 2D low‐crystallinity titanium oxide (2D TiO_x) substrate is reported. Through the metal oxide−support interaction, the 2D TiO_x alters the electronic structure of ruthenium oxide (RuO_x), improving its activity, selectivity, and stability for CER. Specifically, the mass activity of the RuO_x/2D TiO_x electrode is 26.5 and 143.5 times higher than that of the state‐of‐the‐art commercial RuO₂ and DSA, respectively, at an overpotential of 100 mV. Moreover, the selectivity of the RuO_x/2D TiO_x electrode to CER is approximately 96.5%, and it exhibits remarkable durability lasting for over 210 h. Therefore, the 2D TiO_x substrate holds significant potential for improving the dispersion, active site density, and atomic utilization of oxidized sub‐nano noble metal clusters.