Electro-Fenton system, a pivotal advanced oxidation process in wastewater treatment, inherently grapples with dual challenges of O2/solute transfer contradiction and Fe-dissolution deactivation. To surmount these obstacles, a sandwich Pd/C electrode (SE-Pd/C) featuring a three-phase interface (TPI) was fabricated by coating hydrophilic Pd/C catalyst layers onto hydrophobic graphite felt substrate for enhanced hydroxyl radical production through a green H*-mediated Fenton process. SE-Pd/C demonstrated superior performance with an 88.9% TC removal rate, outperforming hydrophilic (HIE, 68.4%) and hydrophobic (HOE, 47.9%) Pd/C electrodes. The underlying rationale for its high performance includes: (1) The TPI in SE-Pd/C optimized the concurrent mass transfer of O2 and TC, enabling an improved electrostatic TC adsorption capacity of 31.2% (versus 27.3% for HIE-Pd/C and 20.3% for HOE-Pd/C), alongside elevated H2O2 production reaching 8.6 g·L−1 (compared to 0.02 g·L−1 for HIE and 2.0 g·L−1 for HOE); (2) The hydrophilic catalyst layer ensured a rich availability of electrochemically active Pd-sites, facilitating H* generation and subsequent H2O2 activation to form •OH (13.4 × 10−12 M·S > 6.7 × 10−12 M·S of HOE > 4.3 × 10−12 M·S of HIE). As H* could be electro-generated from both H+ and H2O, the SE-Pd/C system manifested robust adaptability across a wide pH range of 3−11, consistently achieving ≥ 88.9% TC removal. Thus, this research pioneered the synergy of TPI with the H*-mediated Fenton process, outlining a potent strategy for bolstered treatment of antibiotic-laden wastewater. Display omitted •Atomic H* played a dominant role in the byproduct-free H2O2 activation process.•Introducing TPI concurrently optimized dissolved pollutant/proton and O2 transfer.•Sandwich Pd/C electrode exhibited excellent H2O2 and •OH generation property.•Sandwich Pd/C electrode achieved efficient TC removal in a wide pH range from 3 to 11.