Purpose of Investigation: To explore the ultrasonographic methods towards cleft lip and palate (CLP) in first-trimester. Materials and Methods: 3,795 fetuses were scanned for facial structures including cross section of upper alveolar process, oblique coronal section of upper lip, and postnasal triangle section when measuring nuchal translucency (NT). The abnormal cases underwent ultrasonography for clear diagnosis at 17-18 gestational weeks (GWs), while the negative cases underwent systemic ultrasonography at 20-26 GWs, and followed up until birth. Results: Among the 3795 fetuses, 16 cases had CLP, with an incidence rate as 4.2%; 12 were detected in first trimester, with a detection rate of 75%, and the detection rate of bilateral CLP was 100%, four were missed, with a misdiagnosis rate of 25%, and 12 cases examined at 17-18 GWs met first-trimester diagnosis. Among the four missed cases, two were diagnosed with systemic ultrasonography, and two were diagnosed postnatally. All cases were confirmed after induction of labor or after birth. Conclusions: Ultrasonography in first-trimester could diagnose severe case of CLP.