A major challenge limiting the practical applications of nanomaterials is that the activities of nanostructures (NSs) increase with reduced size, often sacrificing their stability in the chemical environment. Under oxidative conditions, NSs with smaller sizes and higher defect densities are commonly expected to oxidize more easily, since high-concentration defects can facilitate oxidation by enhancing the reactivity with O₂ and providing a fast channel for oxygen incorporation. Here, using FeO NSs as an example, we show to the contrary, that reducing the size of active NSs can drastically increase their oxidation resistance. A maximum oxidation resistance is found for FeO NSs with dimensions below 3.2 nm. Rather than being determined by the structure or electronic properties of active sites, the enhanced oxidation resistance originates from the size-dependent structural dynamics of FeO NSs in O₂. We find this dynamic size effect to govern the chemical properties of active NSs.