In this work, FeO nanoparticle employed as the three-dimensional electrode, were introduced into the electro-oxidation system with peroxydisulfate to improve the tetracycline (TC) degradation. The coprecipitation method prepared FeO was proved to be the irregular sphere-like form through the characterizations of XRD, SEM, N adsorption isotherms, and XPS. By the contrast experiments, the EO-FeO-PDS exhibited the outstanding TC degradation capability, which achieved 86.53% after 60 min treatment with current intensity of 20 mA cm, FeO dose of 0.2 g L, PDS amount of 2 mmol L, initial pH 4.5, and TC concentration of 25 mg L. Besides, the influence of current intensity, FeO dosage, PDS concentration, and beginning pH on the TC degradation was investigated systemically. The consecutive five recycles of FeO demonstrated that a favorable stability for the coupling process. The EO-FeO-PDS could improve the PDS decomposition and HO production. The sulfate and hydroxyl radicals both took charge of the antibiotic degradation as certified by scavenger test. The TC degradation evolution was presented based on the HPLC-MS analyses of degradation byproducts.