A rapid and eco-friendly method, using ultrasound power, was successfully employed to hydrolyze Crambe oil using lipase enzymes directly from castor seeds, in oil-free and in natura forms. A yield of 86% conversion of triglycerides into free fatty acids (FFA) was achieved in 5 minutes using in natura seeds and 73% of conversion when performing the reaction with oil-free seeds. The operational conditions of ultrasound power, mass ratio of buffer solution and oil, catalyst, and total substrate were evaluated using a central composite rotatable design (CCRD). The hydrolysis yield was optimized by Response Surface Methodology. The optimum conditions were approximately 70% of ultrasound power (350 W), 1.79 buffer solution/oil mass ratio, and 0.25 catalyst/substrate mass ratio for in natura seeds. For the oil-free seeds, the optimal conditions found were 68% (340 W) of ultrasound power, 1.67 buffer solution/oil mass ratio, and 0.06 catalyst/substrate mass ratio. Mathematical modeling was applied to the experimental kinetic data, and it was possible to predict FFA concentration values from independent experiments.