The removal of sulfadiazine, sulfamethizole, sulfamethoxazole, and sulfathiazole from aqueous solution by ozonation was studied. The study was conducted experimentally in a semi-batch reactor under different experimental conditions, i.e., varying influent ozone gas concentration, bicarbonate ion concentration, and pH. The results of the study indicated that ozonation could be used to effectively remove the sulfonamides from water. The sulfonamides exhibited moderate reactivity towards aqueous ozone, k O 3 > 2 × 10 4 M −1 s −1 at pH of 2 and 22 °C. The mol of ozone absorbed by the solution per mol of sulfonamides removed varied in the range of 5.5–12.0 with lower ranges representing ozone absorption by the solution at the beginning of the ozonation process whereas higher ratios correspond to >99.9% removal of the target sulfonamides. The removal rate of the sulfonamides improved with bicarbonate ion concentration up to 8 mM but further increase in bicarbonate ion decreased removal efficiency. It was also observed that increasing the pH from 2.0 to 10.0 resulted in enhanced removal of the sulfonamides.