Abstract Although the application of nanozymes is widely studied, it is still a huge challenge to develop a facile strategy to improve enzyme activity. Herein, a novel nanozyme construction strategy is proposed that involves the modulation of surface defects on CeO 2 through controlled atmosphere under mild condition. The CeO 2 prepared in this study is subjected to thermal treatment under various atmospheres, such as H 2 ‐Ar and air, resulting in the formation of tunable oxygen vacancies, as confirmed by high‐resolution transmission electron microscopy (HRTEM), X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), and UV–vis spectroscopy characterizations. The Cb‐H demonstrates peroxidase‐mimicking activity and achieves excellent catalytic performance due to the advantageous nanozyme preparation process, which results in the highest fraction of oxygen vacancies. Therefore, a colorimetric sensor is constructed for the fast and sensitive quantitative analysis of TA with good linearity in the range of 0–2.5 µ m . This work offers strategies for optimizing the catalytic activity of defect‐engineered nanozymes and highlights the practical potential of Cb‐H in the colorimetric detection of tannic acid (TA).