Per- and polyfluoroalkyl substances (PFAS) are highly recalcitrant pollutants in the water environment worldwide. Aqueous film-foaming foam (AFFF) for fire-fighting is a major source of PFAS pollution. However, complete defluorination (i.e., cleaving all C−F bonds into F− ions) of PFAS by a non-thermal technology is rare. The destruction of the PFAS mixture in the complex organic matrix of AFFF is even more challenging. In this study, we designed and demonstrated a UV/sulfite−electrochemical oxidation (UV/S−EO) process. The tandem UV/S−EO leverages the complementary advantages of UV/S and EO modules in (i) PFAS transformation mechanism and (ii) engineering process design (e.g., foaming control, chemical dosage, and energy consumption). At ambient temperature and pressure, The UV/S−EO realized near-complete defluorination and mineralization of most PFAS and organics in AFFF (50−500x diluted, containing up to 200 mg L−1 organic fluorine and >4000 mg L−1 organic carbon). This work highlights the integration of molecular-level insight and engineering design toward solving major challenges of AFFF water pollution and stockpile disposal.