<p>Trifluoroacetic acid (TFA), the shortest per- and polyfluoroalkyl substance, is a ubiquitous molecule and is highly recalcitrant to existing C–F bond cleavage strategies. Here we show the complete mineralization of TFA under ambient conditions via previously undescribed oxidative/reductive tandem reactions. Contrary to the conventional defluorination, the efficacy is attributed to the overlooked nucleophilic oxygen radical anion (O^•−, deprotonated form of hydroxyl radical) oxidation with a rate of 5.1 × 10⁷ M⁻¹ s⁻¹, 50-fold higher than that with the hydrated electron (e_aq⁻). Electron pulse radiolysis experiments, combined with molecular simulations, were used to characterize the generation of CF₃CO₃^2−• intermediates and their subsequent dissociation. The total transformation to F⁻ and CO₃²⁻ is further achieved by e_aq⁻ reduction. Beyond TFA, this intriguing oxidative/reductive tandem strategy also enables mineralization of perfluorobutanoic acid, perfluorohexanoic acid and perfluorooctanoic acid, demonstrating broad applicability across perfluoroacids and halogenated substrates. Its industrial viability is underscored by the use of commercial electron beam irradiation, which achieves rapid defluorination at rates up to 0.27 mol l⁻¹ h⁻¹. These findings describe a promising role for the O^•−/e_aq⁻ tandem pathway for the remediation of short-chain per- and polyfluoroalkyl substances and the degradation of organic halides.</p>