Objective To evaluate the diagnostic value of four-chamber view combined with color Doppler ultrasonography in the screening of fetal congenital heart disease (CHD), and to explore the synergistic diagnostic efficacy of the combined application for structural and functional abnormalities. Methods A retrospective analysis was performed on 100 pregnant women (20-28 weeks of gestation) who underwent prenatal ultrasound screening for fetuses with congenital heart disease in the Department of Ultrasound of Hefei Maternal and Child Health Hospital from January 2022 to January 2023. All subjects were examined by four-chamber view combined with color Doppler ultrasonograpy. All the enrolled fetuses were diagnosed by autopsy after birth or labor induction. If autopsy could not be performed, the diagnosis would be reviewed by two senior physicians with more than 10 years of experience in fetal echocardiography, and the diagnosis would be confirmed by consensus. The diagnostic value of four-chamber view combined with color Doppler ultrasonography was analyzed. Results Fifteen patients were diagnosed with CHD, including 8 cases of ventricular septal defect, 1 case of tetralogy of Fallot, 2 cases of premature ductus arteriosus, 2 cases of tricuspid regurgitation, and 2 cases of complex malformation. The sensitivity of combined examination (93.3%, 14/15) was significantly higher than that of single four-chamber view method (53.3%, 8/15) and color Doppler ultrasonography (80.0%, 12/15) (P<0.05), and the specificity was 98.9%. The combined examination corrected 7 false positive cases of the four-chamber view method (5 cases of false chordal of right ventricle and 2 cases of persistent left superior vena cava), and missed 1 case of small ventricular septal defect (1.2mm in diameter). Conclusion Four-chamber view method combined with color Doppler ultrasonography shows high sensitivity and specificity in the screening of fetal congenital heart disease, which can significantly improve the early diagnosis rate, especially in the detection of functional abnormalities and complex malformations.