Deep eutectic solvents (DESs), promising green solvents, and ultrahigh pressure extraction (UPE) as an effective auxiliary extraction method, have attracted wide attention. In this study, DES was coupled with UPE to efficiently extract baicalin from Scutellaria baicalensis Georgi. First, choline chloride: lactic acid (ChCl-LA, molar ratio 1:1) was selected as the most appropriate DES by comparing the extraction yield of different DESs. Second, the extraction protocol was optimized by response surface methodology (RSM) considering the impacts of ChCl-LA concentration, extraction pressure, extraction time and liquid-solid ratio on the extraction yield. Under the optimal condition (40 vol% water content, extraction pressure of 400 MPa, extraction time of 4 min and a liquid-solid ratio of 110 mL/g), a maximum yield of 116.8 mg/g was achieved, higher than that obtained by the traditional extraction method. The microstructure of the raw and extracted Scutellaria baicalensis Georgi samples according to scanning electron microscope (SEM) images revealed that the dissolution of chemical components was enhanced from the disrupted root tissues after DESs-UPE. DESs coupled with UPE could effectively extract the baicalin from Scutellaria baicalensis Georgi as a rapid and efficient extraction method.