The widespread detection and potential adverse effects of antibiotics in the aquatic environment call for effective treatment technology. Electro-Fenton is a promising strategy, but the preparation of efficient and stable cathodes is still challenging. In this study, a novel metal-organic framework (MOF)-derived N-doped cathode Fe/Cu-C400Ar was synthesized successfully for the degradation of ceftazidime (CAZ) in heterogeneous electro-Fenton (hetero-EF) system. The doping of copper could enhance electrocatalysis with a high electrochemical surface active area and low resistance. Fe/Cu-C400Ar cathode achieved CAZ removal efficiency of 99.5 ± 0.4% within 120 min, and it exhibited excellent stability after six recycle runs. Quenching experiments and electron paramagnetic resonance (EPR) tests proved that the primary species was hydroxyl radical during the CAZ degradation. In addition, the degradation pathway of CAZ was proposed including the cleavage of the pyridine ring and the shedding of the thiazole ring. Moreover, the prediction of intermediates toxicity by Ecological Structure Activity Relationships (ECOSAR) software indicated the environmentally friendly features of the CAZ degradation process. This study provided a promising cathode for the electrocatalytic degradation of antibiotic wastewater in hetero-EF system.