A free-of-dust pollution extraction method combined-homogenate and ultrasonic cavitation system, namely, homogenate-combined ultrasonic cavitation synergistic extraction (HUCSE), was proposed for the efficient extraction of flavonoids from Cinnamomum camphora leaves. Response surface methodology of Box-Behnken design was employed to optimize the HUCSE process, and the optimum operation conditions attained with an extraction yield of 7.95 ± 0.27 mg/g were ethanol concentration 76%, homogenate/ultrasonic time 25 min, solvent-to-solid ratio 22 mL/g, and ultrasonic power 240 W. A second-order kinetic mathematical methodology was performed to depict the behaviors of HUCSE and heat reflux extraction method. The results suggested that the developed HUCSE is an efficient and green method for the extraction of C. camphora flavonoids or other plant natural products, where the obvious higher parameters of extraction capacity at saturation, second-order extraction rate constant, and original extraction rate were obtained when compared to the heat reflux method. The antioxidant activity assays in vitro showed that the C. camphora flavonoids possessed strong antioxidant activity and are promising to be applied as a natural alternative antioxidant.