A novel advanced oxidation technology of ozone and ferrate (ozone/Fe (VI)) was investigated and used to degrade micropollutants (e.g., sulfamethoxazole (SMX), diclofenac sodium (DCF)) in this study. The results demonstrated that the ozone/Fe(VI) process can rapidly and efficiently degrade SMX and DCF. The SMX and DCF degradation was substantially accelerated by increasing the Fe(VI) dosage (5 to 25 μM) or ozone concentration (10 to 52 μM), up to 77.0 % and 82.7 % of SMX and DCF were obtained, respectively. The removal efficiencies of SMX and DCF was higher in acidic conditions, and decreased from 98.4 % to 44.7 % and from 94.3 % to 62.9 %, respectively, at pH 5–9 in the presence of buffer. Besides, CO32−, Cl−, and HA had a little negative effect on SMX and DCF removal, and the ozone/Fe(VI) process still obtained high degradation efficiency (>64.5 %) for SMX and DCF in real water. On the basis of the finding of scavenging and probe experiments, ozone, Fe(VI), OH, and Fe(IV)/Fe(V) species were identified as the predominant oxidants for SMX and DCF degradation. Sixteen and eighteen transformation products (TPs) of SMX and DCF in ozone/Fe(VI) process were detected by UPLC-QTOF-MS. Then, the reaction pathways of SMX and DCF were proposed by Fukui function analysis and TPs identification. Using the ECOSAR software, the ecotoxicity of SMX, DCF, and their TPs were evaluated. These findings might provide useful information and a theoretical foundation for the application of ozone/Fe(VI) process in water treatment.