Electrochemical advanced oxidation processes (EAOPs) based on natural air diffusion electrode (NADE) promise efficient and affordable advanced oxidation water purification, but the sustainable operation of such reaction systems remains challenging due to severe cathode electrowetting. Herein, a novel floating cathode (FC) composed of a stable hydrophobic three-phase interface was established by designing a flexible catalytic layer of FC. This innovative electrode configuration could effectively prolong the service life of the cathode by mitigating the interference of H bubbles from the hydrogen evolution reaction (HER), and the HO production rate reached 37.59 mg h·cm and realize a long-term stable operation for 10 h. Additionally, an FC/carbon felt (CF) dual-cathode electro-Fenton system was constructed for in situ sulfamethoxazole (SMX) degradation. Efficient HO production on FC and Fe(III) reduction on CF were synchronously achieved, attaining excellent degradation efficiency for both SMX (ca. 100%) with 2.5 mg L of Fe(Ⅱ) injection. For real wastewater, the COD removal of the FC/CF dual-cathode electro-Fenton system was stabilized at exceeding 75%. The practical application potential of the FC/CF dual-cathode electro-Fenton system was also demonstrated for the treatment of actual landfill leachate in continuous flow mode. This work provides a valuable path for constructing a sustainable dual-cathode electro-Fenton system for actual wastewater treatment.