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In this study, we studied the degradation kinetics of a common iodine contrast agent, diatrizoate, by ozone and the formation of disinfection by-products (DBPs) in the sequential chlorination. Effects of ozone concentration, solution pH, and bromide concentration on diatrizoate degradation were evaluated. The results indicate that diatrizoate can be effectively degraded (over 80% within 1 h) by ozone, and the degradation kinetics can be well described using the pseudo-first-order kinetic model. The pseudo-first-order rate constant (kobs) of diatrizoate degradation significantly increased with increasing ozone concentration and decreasing bromide concentration. The kobs kept increasing with the increase of pH value and reached a maximum of 6.5 (±0.05) × 10−2 min−1 at pH 9. As the ozone concentration gradually increased from 0.342 to 1.316 mg/L, the corresponding kobs of diatrizoate degradation increased from 1.76 (±0.20) × 10−3 to 4.22 (±0.3) × 10−2 min−1. The bromide concentration exhibited a strong inhibitory effect on diatrizoate degradation because of the competition for ozone with diatrizoate. Trichloromethane was the only detected DBP in the subsequent chlorination in the absence of bromide. However, in the presence of bromide, six other DBPs were detected, and bromochloroiodomethane and tribromomethane became the major products with concentrations 1–2 orders higher than those of the other DBPs. In order to provide safe drinking water to the public, water should be maintained at circumneutral pH values and low bromine concentrations ( 7.; •OH played a major role in diatrizoate degradation during ozonation.; Bromide can strongly inhibit diatrizoate degradation because of the competition for ozone with diatrizoate.; The formation of DBPs can be controlled at circumneutral pH and low bromine concentrations (