For the first time, response surface methodology (RSM) using a Box-Behnken Design (BBD) was employed to optimize the conditions for ultrasonic assisted extraction (UAE) of antioxidants from Chinese sumac (Rhus typhina L.) fruits. Initially, influencing factors such as liquid-solid ratio, duration of ultrasonic assisted extraction, pH range, extraction temperature and ethanol concentration were identified using single-factor experiments. Then, with respect to the three most significant influencing factors, the extraction process focusing on the DPPH· scavenging capacity of antioxidants was optimized using RSM. Results showed that the optimal conditions for antioxidant extraction were 13.03:1 (mL/g) liquid-solid ratio, 16.86 min extraction time and 40.51% (v/v) ethanol, and the desirability was 0.681. The UPLC-ESI-MS analysis results revealed eleven kinds of phenolic compounds, including four major rare anthocyanins, among the antioxidants. All these results suggest that UAE is efficient at extracting antioxidants and has the potential to be used in industry for this purpose.