Antibiotics are a new class of organic compounds that have antibacterial and anti-inflammatory effects in the clinic, but their widespread use has serious adverse effects on the natural water environment. Sulfadiazine (SDZ) is a typical kind of antibiotic, and the treatment effect of the traditional biochemical degradation process has not been ideal. Thus, in order to find a more efficient and clean degradation method, we investigated the degradation effect of ozone/persulfate (O-3/PMS) advanced oxidation process (AOPs) on SDZ in prepared water and natural water for the first time and compared it with the experimental results of ozone (O-3) and ozone/ultraviolet (O-3/UV) methods. The experimental results showed that when the initial mass concentration of O-3 was 3 mg/L, the initial mass concentration of SDZ was 10 mg/L, the temperature was 25 degrees C, the pH was 6.8 +/- 0.1, the K-obs of O-3/PMS was 0.2497 min(-1), and the K-obs values of O-3 and O-3/UV were 0.1242 and 0.1328 min(-1), respectively. The time required for O-3/PMS to degrade SDZ below the detection limit (0.01 mg/L) was about 7 min shorter than that of O-3 and O-3/UV. It was found that in O-3/PMS, the increase in the initial mass concentration of SDZ inhibited its degradation, and the increase in the initial mass concentration of ozone increased the degradation rate of sulfadiazine. The degradation process conformed to the pseudo-first-order reaction kinetic equation. O-3/PMS was suitable for weak alkaline environments. When pH was 9, the concentration of free radicals was the highest. Excessive alkalinity led to mutual quenching of free radicals and reduced the degradation rate. The mineralization effect of O-3/PMS was slightly worse than that of the O-3/UV process, but O-3/PMS effectively degraded SDZ and fluorescent substances dissolved in water, with good prospects in practical engineering applications.