Superoxide, a potentially toxic by-product of cellular metabolism, may contribute to tissue injury in many types of human disease. Here we show that a tris-malonic acid derivative of the fullerene C₆₀ molecule (C₃) is capable of removing the biologically important superoxide radical with a rate constant (k_C3) of 2 × 10⁶ mol⁻¹ s⁻¹, approximately 100-fold slower than the superoxide dismutases (SOD), a family of enzymes responsible for endogenous dismutation of superoxide. This rate constant is within the range of values reported for several manganese-containing SOD mimetic compounds. The reaction between C₃ and superoxide was not via stoichiometric “scavenging,” as expected, but through catalytic dismutation of superoxide, indicated by lack of structural modifications to C₃, regeneration of oxygen, production of hydrogen peroxide, and absence of EPR-active (paramagnetic) products, all consistent with a catalytic mechanism. A model is proposed in which electron-deficient regions on the C₆₀ sphere work in concert with malonyl groups attached to C₃ to electrostatically guide and stabilize superoxide, promoting dismutation. We also found that C₃ treatment of Sod2^−/− mice, which lack expression of mitochondrial manganese superoxide dismutase (MnSOD), increased their life span by 300%. These data, coupled with evidence that C₃ localizes to mitochondria, suggest that C₃ functionally replaces MnSOD, acting as a biologically effective SOD mimetic.