In this work, the photolysis of enrofloxacin (ENR), pefloxacin (PEF), and sulfaquinoxaline (SQX) in aqueous solution by UV combined with H2O2 or ferrous ions (Fe(II)), as well as Fenton (Fe(II)/H2O2) processes, was investigated. In addition, the toxicity of the final reaction solution after UV/H2O2/Fe(II) treatment toward zebrafish embryos was determined. The degradation of the test compounds followed pseudo-first-order reaction kinetics. The optimum concentrations of H2O2 for ENR, PEF and SQX removal under UV/H2O2 treatment were 20, 20 and 5 mM, respectively. The optimum concentrations of Fe(II) for ENR, PEF and SQX removal in the UV/Fe(II) system were 0.25, 10, and 1 mM, respectively. For the UV/H2O2/Fe(II) system, pH = 3 is the best initial pH for the degradation of ENR, PEF and SQX with the degradation efficiencies at 100%, 79.1% and 100% after 180 min, respectively. Considering the degradation rate and electrical energy per order of the test compounds, the UV/H2O2/Fe(II) process was better than the UV/H2O2 and UV/Fe(II) processes because of the greater OH generation. Based on major transformation products of ENR, PEF, and SQX detected during UV/H2O2/Fe(II) treatment, the probable degradation pathway of each compound is proposed. The fluorine atom of ENR and PEF was transformed into fluorine ion, and the sulfur atom was transformed into SO2/SO42−. The nitrogen atom was mainly transformed into NH3/NH4+. Formic acid, acetic acid, oxalic acid, and fumaric acid were identified in the irradiated solutions and all the test compounds and their intermediates can be finally mineralized. In addition, after the UV/H2O2/Fe(II) process, the acute toxicity of the final reaction solutions on zebrafish embryos was lower than that of the initial solution without any treatment. In summary, UV/H2O2/Fe(II) is a safe and efficient technology for antibiotic degradation. Display omitted •ENR, PEF and SQX can be finally mineralized under UV/H2O2/Fe(II)•OH played a vital role for the UV/H2O2/Fe(II) degradation of pollutants.•The degradation pathways for ENR, PEF and SQX were proposed under UV/H2O2/Fe(II).•The acute toxicity on zebrafish embryos decreased after UV/H2O2/Fe(II) treatment.