Background Central nervous system (CNS) anomalies are an important factor of neonatal deaths. Three-dimensional (3D)/4D ultrasound (US) has an advantage over the conventional 2D US as it provides additional multiple options like multiplanar view, tomographic view, and surface rendering view leading to accurate diagnosis of fetal congenital anomalies. Aim The aim of this study was to evaluate the role of the 4D US in the diagnosis of in utero congenital CNS anomalies. Patients and methods The current study was conducted on 30 pregnant women with suspected congenital CNS anomalies by 2D US in Tanta University Hospitals. All the patients were subjected to 2D and 4D US examination in cases with suspected anomalies by 2D US. Results Out of 30 anomalies, two (6.5%) anomalies were lobar holoprosencephaly; six (20%) anomalies were anencephaly, three (10%) anomalies were exencephaly, one (3.5%) anomaly was aqueductal stenosis, three (10%) anomalies were chiari malformation with its two types I and II, and three (10%) anomalies were Dandy–Walker. Three anomalies were hydranencephaly (10%), three (10%) meningocele, one (3.5%) spina bifida, and two cases were obstructive hydrocephalus distal to the 4th ventricle (obstruction of foramen of luschka and magendie) (6.5%). As regards brain anomalies, sensitivity of 4D US=96.4%, specificity of 4D US=100%, positive predictive value=100%, negative predictive value=50.0%, and accuracy=96%. So, 4D US is more superior to 2D US in demonstrating anomalies of the CNS (through multiplanar view and tomographic views), which may affect the postnatal outcome. 4D US offers precise demonstration of normal and abnormal fetal structures through its different modes, so it helps in accurate prenatal diagnosis of CNS anomalies. Conclusion 4D US is considered now an important diagnostic tool in fetal medicine as it provides many advanced diagnostic options such as multiplanar view or tomographic imaging, volume calculation, and surface rendering mode, which aided in early diagnosis of fetal anomalies and improved postnatal outcome.