<p>Perfluorooctane sulfonate (PFOS) resists complete defluorination under ambient conditions. We developed a mechanochemical (MC) method using <i>α</i>-Al₂O₃ and Fe that achieved complete defluorination of PFOS. Among the tested metal oxides and zero-valent metals, the combination of <i>α</i>-Al₂O₃ and Fe enabled complete defluorination of PFOS while preventing overreduction of the sulfonate group to generate toxic H₂S. Instead, the reaction produced SO₃²⁻, F⁻, and amorphous carbon as the main products. The defluorination rate in this MC system was more than three times faster than that reported for other MC systems. This method could not only be applied to PFOS alternatives but also enabled the defluorination of PFOS in soil. During ball milling, the <i>in situ</i> generated coordinative unsaturated Fe³⁺ and Al³⁺ on the surface of the milling reagents bound the sulfonate group of PFOS to promote desulfonation. Fe has a moderate reducing ability that facilitated reductive desulfonation and subsequent defluorination while simultaneously inhibiting the overreduction of the sulfonate group. <i>α</i>-Al₂O₃ suppressed Fe aggregation and critically inhibited the protonation of the desulfonation fragment (i.e., C₈F₁₇⁻) owing to the small amount of surface OH⁻/H₂O. This ability enhanced the electron transfer from Fe to C₈F₁₇⁻, leading to complete defluorination without the generation of hydrofluorocarbons.</p>