Purpose: This study aimed to evaluate the effectiveness of the four-section approach using two-dimensional sonography in diagnosing Pierre Robin sequence (PRS) during second-trimester screening. Methods: A prospective study was conducted on low-risk pregnant women undergoing routine mid-trimester screening. Cases with suspected micrognathia prenatally were included and examined using the four-section approach. Initially, we measured the inferior facial angle (IFA) for fetuses suspected of having micrognathia. Subsequently, in the oblique coronal section via the oral fissure, we examined the continuity of the hard and soft palate line. Finally, dynamic scanning of both the sagittal and coronal sections of the mandible was performed to confirm whether the echogenic tongue was displaced posteriorly. All fetuses diagnosed with PRS were followed up through autopsy and postnatal evaluation. Results: Forty-three fetuses were initially subjectively suspected of having micrognathia by sonographers. After objective IFA measurement, 25 cases had an IFA < 50 degrees, while 18 had an IFA > 50 degrees. Among the 25 cases with IFA < 50 degrees, we identified 13 cases of PRS with micrognathia, cleft palate (CP), and glossoptosis. However, one case failed to be diagnosed prenatally because it had micrognathia and CP but no glossoptosis. Eleven cases had neither CP nor glossoptosis yet exhibited other malformations. Among the 18 fetuses with IFA > 50 degrees, 15 cases were normal, while three cases had other deformities. In this study cohort, no false-positive results were found. The four-section approach for diagnosing PRS showed a sensitivity of 92.9%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 91.7%. Conclusion: The four-section method proved highly effective in assessing PRS during second-trimester sonographic scans. The combined evaluation of micrognathia and glossoptosis can remarkably enhance the accuracy of prenatal PRS diagnosis.