The study of anionic redox in layered-oxide cathodes for Na-ion batteries (NIBs) has been extensive, aiming to attain high-energy density. The involvement of Mn4+ or Ru5+ oxidation states is known to be crucial for the anionic O2 −/O− reaction during Na+ de/intercalation. Nevertheless, our findings indicate that anionic redox can activate in Ru-based layered-oxide cathodes prior to complete Ru4+/Ru5+ oxidation. By employing first-principles calculation and experimental techniques, we disclose that additional Na+ deintercalation from P2-Na0.33[Mg0.33Ru0.67]O2 relies on anionic oxidation after extracting 0.33 mol Na+ from P2-Na0.67[Mg0.33Ru0.67]O2, concomitant with cationic oxidation of Ru4+/Ru4.5+. Specifically, only the oxygen adjacent to 2Mg/1Ru is implicated in anionic redox during Na+ de/intercalation, indicating that the Na–O–Mg arrangement in the P2-Na0.33[Mg0.33Ru0.67]O2 structure significantly reduces the thermodynamic stability of anionic redox compared to cationic redox. Through O anionic and Ru cationic reactions, P2-Na0.67[Mg0.33Ru0.67]O2 demonstrates a substantial specific capacity of ∼172 mA h g− 1 and exceptional power capability, facilitated by facile Na+ diffusion and reversible structural changes during charge/discharge. These findings propose an innovative strategy to enhance anionic redox activity by modifying the local oxygen environment, paving the way for high-energy-density cathode materials in NIBs.