Display omitted •A novel UV-EFCM filtration system was developed.•Low-concentration antibiotic contaminant was efficiently degraded.•The antibacterial activity was thoroughly eliminated with UV light pretreatment.•Specific energy consumption of the integrated system was significantly reduced.•Integrated system has the potential to tackle the problem of antibiotic pollution. Antibiotics, especially halogenated antibiotics, which account for nearly 40% of the total antibiotics in China, pose great environmental risks; however, the superior stability of C–F bond and low concentrations hinder their degradation, indicating the need for developing of highly efficient treatment technologies. There is an additional concern that some degradation products could be as active/toxic as or even more than their parent compound. The stable C–F bond can be relative easily cleaved by UV light irradiation, which could come from sunlight. Herein, a novel UV-driven electro-Fenton catalytic membrane (UV-EFCM) filtration system that favors resistance elimination and efficient degradation of low-concentration antibiotics is proposed for the first time. The photo-electrochemical/electro-Fenton (PEC/EF) coupling reaction is synchronously conducted in a sequential filtration system. Almost complete degradation and high mineralization (78.4 ± 9.1%) of florfenicol were achieved at a concentration of as low as 14 µM with the hydraulic retention time of 0.98 h during the UV-EFCM filtration system. Complete elimination of its antibacterial activity, and significant defluorination improvement (56 ± 3.6%) compared to electro-Fenton filtration process (11 ± 5.3%) were achieved due to the prior cleavage of the stable C–F bond with antibiotic potency under UV light pretreatment. This study thus proposes a novel UV-EFCM filtration system, which couples PEC and EF with a potential to tackle the environmental problems associated with antibiotic pollution.