Degradation by high frequency ultrasound (US) of the endocrine disruptor, benzophenone-3 (BP-3) is a promising treatment process as it does not need additives and does not generate waste. In this paper the variables affecting this process were studied. The frequency effect on initial degradation rates was analyzed for various frequencies between 215 and 1,134 kHz, and an optimum frequency of 574 kHz was found in this range. Power density had a positive effect on degradation rates over the whole work range. Kinetics adjusted statistically well to a pseudolinear kinetic model. According to these results and those for degradation in presence of radical scavengers, a conclusion was made that US BP-3 degradation was taking place in the bubble/liquid interphase. Toxicity test was conducted by Microtox methods, finding an EC50 for 5 min of 1.7 mg/L, and for 15 min of 2.07 mg/L. Toxicity profile along degradation path showed a decrease at the beginning growing after 30% of BP-3 degradation. Four possible degradation byproducts were found by gas chromatography–mass spectrometry (GC-MS) analysis, and a degradation path was proposed.