Ultrasound is an emerging decontamination technology with potential use in the global food processing industry. In the present study, we explored power ultrasound for processing aqueous aflatoxin B (AFB). AFB was degraded by 85.1% after 80 min of ultrasound exposure. The reaction products of AFB were identified and their molecular formulae elucidated by ultra-high-performance liquid chromatography Q-Orbitrap mass spectrometry. Eight main reaction products were found, and their structures were clarified by parental ion fragmentation. Two degradation pathways were proposed according to the degradation product structures: One involved the addition of H• and OH• radicals, whereas the other involved HO epoxidation and H•, OH•, and HO oxidation of AFB. Ultrasound treatment significantly reduced AFB bioactivity and toxicity by disrupting the C8=C9 double bond in the furan ring and modifying the lactone ring and methoxy group.