Amoxicillin (AMO) degradation was investigated using electrolysis, ozonation, and electro-peroxone (E-peroxone) process. E-peroxone process was found to be the most effective for AMO degradation. 67.8% total organic carbon (TOC) mineralization was obtained after 60 min by E-peroxone process. In comparison, only 47.3% and 3.1% TOC mineralization were obtained using individual ozonation and electrolysis process, respectively. It was found that hydroxyl radical production and O3 utilization were both enhanced in E-peroxone process. The effect of pH on E-peroxone process was investigated, and the highest AMO removal rate was obtained at pH= 9, indicating pH control was crucial in E-peroxone process. In addition, more oxidation typical intermediates were identified in E-peroxone process than ozonation process using UPLC-MS/MS. Different pathways of AMO degradation were proposed, involving the hydroxylation of the benzoic ring and N, the four-membered β-lactamic ring opening, the oxidation of S, and other bond cleavage reactions. All these results above indicated that the introduction of electrolysis in ozonation has enhanced AMO cleavage and hence its degradation.