Consumer demand for safe and nutritious fruit juices has led to the development of a number of food processing techniques. To compare the effect of two processing technologies, thermo-sonication (TS) and ultra-high pressure (UHP), on the quality of mango juice, fresh mango juice was treated with TS at 25, 45, 65 and 95 °C for 10 min and UHP at 400 MPa for 10 min. The phenolic profile of mango was also analyzed using the newly developed ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-mass spectrometry (UPLC-Q-TOF-HRMSⁿ) and, based on this result, the effect of TS and UHP on the phenolics of mango juice was evaluated. Both treatments had minimal effects on the ^oBrix, pH, and titratable acidity of mango juice. The residual activities of three enzymes (polyphenol oxidase, peroxidase, and pectin methylesterase), antioxidant compounds (vitamin C, Total phenolics, mangiferin derivatives, gallotannins, and quercetin derivatives) and antioxidant activity sharply decreased with the increase in the temperature of the TS treatment. Nevertheless, the UHP treatment retained antioxidants and antioxidant activity at a high level. The UHP process is likely superior to TS in bioactive compounds and antioxidant activity preservation. Therefore, the mango juice products obtained by ultra-high-pressure processing might be more beneficial to health.