Ultrasounds are considered an emerging technology in the wine industry. Concretely, in 2019, the International Organization of Vine and Wine (OIV) officially approved their use for the treatment of crushed grapes to increase the level of phenolic compound extraction. The main objective of this study was to validate an untargeted metabolomics approach as an analytical tool for identifying novel markers associated with sonication. To do so, the influence of a sonication treatment on the metabolic profile was studied in four typically commercial varietal wines, i.e., two red wines from 'Syrah' and 'Cabernet Sauvignon' grapes and two white wines from 'Macabeo' and 'Airén' grapes. A robust classification and prediction model was created employing supervised techniques such as partial least-squares discriminant analysis (PLS-DA). The findings indicated that the grapes subjected to high-power ultrasound conditions experienced cell wall disruption due to the cavitation phenomenon, resulting in significant changes in various phenolic compounds (including hydroxycinnamic acids and flavonoids) present in these wines compared to wines from non-sonicated grapes. Additionally, new metabolites were tentatively identified through untargeted metabolomics techniques. This study represents the successful application of the untargeted metabolomics approach employing a UHPLC-QTOF system to discern how grape sonication affects bioactive secondary metabolites in wines.