The presence of antibiotic sulfadiazine (SFD) poses threats to the ecosystem and human health, and traditional wastewater treatment processes are not ideal for sulfadiazine removal. Therefore, it is urgent to develop treatment processes with high efficiency targeting sulfadiazine. This study investigated the degradation and mineralization mechanisms of SFD by ozone-based catalysis processes including ozone/persulfate (PS) and ozone/peroxymonosulfate (PMS). The degradation, mineralization and byproducts of SFD were monitored by HPLC, TOC and LC/MS, respectively. SFD was efficiently removed by two ozone-based catalysis processes. Ozone/PMS showed high efficiency for SFD removal of 97.5% after treatment for 1 min and TOC reduction of 29.4% after treatment for 20 min from wastewater effluents. SFD degradation was affected by pH, oxidant dosage, SFD concentration and anions. In the two ozone-based catalysis processes, hydroxyl radicals (OH•) and sulfate radicals (SO4•−) contributed to the degradation of SFD. The degradation pathways of SFD under the two processes included hydroxylation, the opening of the pyrimidine ring and SO2 extrusion. The results of this study demonstrate that the two ozone-based catalysis processes have good potential for the elimination of antibiotics from water/wastewater effluents.