Abstract2D transition metal halide oxides (TMHOs) have attracted much interest due to their intriguing ferroelectrics and excellent nonlinear optics, however, their susceptibility to oxidation makes their basic research and practical application a challenge. Therefore, it is crucial to understand the oxidation mechanism and explore effective strategies for protection. Here, taking van der Waals (vdWs) ferroelectric NbOI2 as an example, oxidation mechanisms and tuning the oxidation behaviors of NbOI2 and its heterostructures by a variety of in situ experiments and first‐principles calculations are discovered. The ambient‐pressure X‐ray photoelectron spectra reveal a self‐limiting oxidation in isolated NbOI2, driven by spontaneously formed iodine vacancies that react with oxygen molecules due to their lower formation and adsorption energies. For the heterostructures with a lower Fermi level (such as WSe2) than transition state VI@NbOI2 (NbOI2 rich in I‐vacancies), the charge transfer from NbOI2 to WSe2 drives the continuous and complete oxidation of NbOI2 flakes. Moreover, the heterostructures with a higher Fermi level (such as graphene) than VI@NbOI2 can weaken the oxidation of NbOI2. By linking the energy band structures to oxidation behavior, the work offers a new oxidation mechanism of 2D air‐sensitive materials and a crucial strategy for improving their chemical stability.
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