This study investigates the ultrasound-assisted extraction of flavonoids from Malaysian cocoa shell extracts, and optimization using response surface methodology. There are three variables involved in this study, namely: ethanol concentration (70–90 v/v %), temperature (45–65 °C), and ultrasound irradiation time (30–60 min). All of the data were collected and analyzed for variance (ANOVA). The coefficient of determination (R2) and the model was significant in interaction between all variables (98% and p < 0.0001, respectively). In addition, the lack of fit test for the model was not of significance, with p > 0.0684. The ethanol concentration, temperature, and ultrasound irradiation time that yielded the maximum value of the total flavonoid content (TFC; 7.47 mg RE/g dried weight (DW)) was 80%, 55 °C, and 45 min, respectively. The optimum value from the validation of the experimental TFC was 7.23 ± 0.15 mg of rutin, equivalent per gram of extract with ethanol concentration, temperature, and ultrasound irradiation time values of 74.20%, 49.99 °C, and 42.82 min, respectively. While the modelled equation fits the data, the T-test is not significant, suggesting that the experimental values agree with those predicted by the response surface methodology models.