A novel size dependence in the adsorption reaction of multiple O₂ molecules onto anionic silver clusters Ag_n^- (n = 1−5) is revealed by gas-phase reaction studies in an rf-ion trap. Ab initio theoretical modeling based on DFT method provides insight into the reaction mechanism and finds cooperative electronic and structural effects to be responsible for the size selective reactivity of Ag_n^- clusters toward one or more O₂. In particular, Ag_n^- clusters with odd n have paired electrons and therefore bind one O₂ only weakly, but they are simultaneously activated to adsorb a strongly bound second oxygen molecule. For the clusters Ag₃O₄^- and Ag₅O₄^-, this cooperative effect results in a superoxo-like, doubly bound O₂ subunit with potentially high activity in catalytic silver cluster oxidation processes.