Congenital abnormalities are important causes of morbidity and mortality in children and significantly add to the burdens on healthcare in developing countries. Unfortunately, there remains a paucity of information on congenital birth defects in most developing countries. This is a 4-year prospective study that assessed the patterns and predictors of congenital anomalies among newborns at the Enugu State University Teaching Hospital, Nigeria. In total, 5830 deliveries were recorded, of which 38 had congenital anomalies, giving an incidence rate of 6.5/1000 live births. Fifty-two newborns were enrolled as nested controls. Factors significantly associated with congenital anomalies were low birth weight (p = 0.009), low socio-economic class (p = 0.011), lower maternal educational attainment (p = 0.009), parity of ≥ 5 (p = 0.002), febrile illness (p = 0.001) and the use of local concoction in index pregnancy (p = 0.009). More than half of the anomalies reported involved the musculoskeletal system. Occurrence of congenital anomalies may be prevented by curtailing risk factors identified in this study.