The oxidation of ibuprofen (IBP) in water was evaluated using oxidative treatments: ozonation, sonication, hydrogen peroxide addition and combinations of these processes. After 20 minutes of treatment, ozone coupled with hydrogen peroxide at pH 7, 15 °C, an ozone dose of 16 mg/L and a hydrogen peroxide concentration of 7.1 mg/L was found to have the highest IBP (95%) and chemical oxygen demand (COD) (41%) removals. A synergistic effect was observed for the combined ozonation/sonication process, which might be explained by an improved mass transfer of ozone in the solution due to the presence of ultrasonic pressure waves. Transformation products were detected in the treated solutions. The nature of five of these products was confirmed by liquid chromatography–mass spectrometry (LC-MS), including 4-isobutylacetophenone (4-IBAP), oxo-IBP, 4-acetylbenzoic acid, 4-ethybenzaldehyde and oxalic acid. In addition, COD analyses for each experiment showed that the ratio of %COD removal to %IBP removal was highest with sonication; suggesting that this oxidative process offers other mechanisms of removal which may lead to further degradation of products formed. This study presents the first data on removal of IBP by sonication coupled to ozonation and provides some insight into the potential of this combined treatment approach for the removal of contaminants of emerging concern.