Ensuring drinking water safety remains a critical challenge, particularly when treating complex water sources, due to secondary pollution caused by active chemical additives. Herein, a novel CO-responsive smart wood scaffold that leverages non-toxic CO activation is developed to achieve highly efficient removal of carcinogenic natural organic matter (NOM) and broad-spectrum microbial disinfection without requiring additional chemical agents. Unlike conventional water purification techniques that face a safety-efficacy trade-off, the multi-stage CO-responsive wood scaffold offers exceptional tunability in NOM abatement across diverse environmental conditions, including variable water chemistry, NOM composition, high salinity, and real-world water sources. The purified water meets stringent drinking water standards (e.g., UV reduction, dissolved organic carbon removal, and bacterial elimination). It is found that the highly efficient NOM adsorption mainly originates from the strong and stable CO-triggered cation-π interaction between the scaffold surface and aromatic NOM groups, as revealed via high-resolution mass spectrometry and direct intermolecular force measurements. This ecofriendly and contamination-free CO-responsive strategy provides a transformative approach to overcoming secondary pollution challenges in water purification, offering a scalable and sustainable platform for environmental applications and beyond.