In Electro-Fenton (EF) processes, the use of iron as a catalyst under acidic conditions results in increased costs and potential secondary pollution. To address these issues, we developed a CuFeV layered double hydroxide (LDH) coating on graphite felt (GF) (CuFeV LDH@GF) that offers an effective performance across a broad pH range without causing metal pollution. The CuFeV LDH@GF cathode exhibited a good oxygen reduction performance, high stability, and an efficient removal of levofloxacin (LEV) over a wide pH range (pH = 3–10). The simultaneous presence of Cu2+/Cu3+, Fe2+/Fe3+, and V4+/V5+ redox pairs played a crucial role in facilitating interfacial electron transfer, thereby enhancing the production and subsequent activation of H2O2 within the system. The apparent rate constant (kapp) of LEV removal under neutral conditions with the CuFeV LDH@GF electrode was more than twice that of the raw GF electrode. This improvement can be attributed to the CuFeV LDH coating, which increased the generation of hydroxyl radicals (•OH) from 0.64 to 1.27 mM. Importantly, the CuFeV LDH@GF electrode maintained its efficiency and stability even after 10 reuse cycles. Additionally, GC–MS analyses revealed the degradation of intermediate compounds, which included cyclic and aliphatic compounds. This study provides significant insights into the synergistic effects of trimetallic LDHs, contributing to the development of high-performance cathodes.