In this study, a simultaneous water extraction process for baicalin, wogonoside, and chlorogenic acid has been optimized. The effect of extraction temperature, extraction time, and liquid−solid ratio was scrutinized by single factor experiments and further analyzed by Box−Behnken design (BBD) approach using response surface methodology (RSM). The extraction yield of investigated compounds was determined by high performance liquid chromatography (HPLC). Single-factor experiments and response surface analysis results revealed that the optimized conditions are: Liquid to solid ratio 25:1 (mL/g), extraction temperature 93 °C, extraction time 2.4 h, and the extraction cycle two. Importantly, it has been noted that under the above conditions, concentrations of baicalin, wogonoside, and chlorogenic were 0.078, 0.031, and 0.013 mg/mL, respectively, and the overall desirability (OD) value was 0.76 which was higher than the non-optimized conditions and the deviation from the predicted OD value was only 2.44%. Conclusively, it has been suggested that the model was stable and feasible, and fit for extraction of baicalin, wogonoside, and chlorogenic acid from Scutellariae Radix and Lonicerae (L.) japonicae Flos.