Zirconium oxide cluster anions Zr(x)O(y)(-) are prepared by laser ablation and are reacted with n-butane in a fast flow reactor under near room temperature conditions. A time-of-flight mass spectrometer is used to detect the cluster distribution before and after the reactions. Observation of a hydrogen atom pickup product Zr(2)O(8)H(-) indicates a C-H activation reaction: Zr(2)O(8)(-) + n-C(4)H(10) → Zr(2)O(8)H(-) + C(4)H(9). Density functional theory calculations predict that the oxygen-very-rich cluster Zr(2)O(8)(-) contains one mononuclear oxygen-centered radical (O(-)(•)), which leads to a high C-H activation reactivity, in agreement with the experiments. This study provides one example for how the highly oxidative O(-)(•) radical may be generated by adsorption of O(2) onto unreactive metal oxide clusters.