Introduction: Malformations of the central nervous system (CNS), the type of congenital defect second only to cardiac malformations, cause infant disability and mortality. Objective: The aim of the study was to evaluate the incidence of congenital malformations of the CNS in newborns treated at a regional public hospital in Southern Mexico and explore the associated factors. Methods: This descriptive study included 113 newborns with CNS malformations. A specific diagnosis was provided and information was obtained from the parents in relation to age, schooling, occupation, prenatal control, intake of folic acid, and exposure to pesticides. A database was created in the statistical program Epi Info version 3.4.3 to carry out univariate and bivariate analyses using the Chi-square test, with significance considered at p < 0.05. Results: The most frequent malformations were hydrocephalus (45.1%), Arnold-Chiari (32.7%), and encephalocele (8.0%). Of the 113 newborns herein examined, a greater percentage of congenital malformations was found when the first pregnancy took place in mothers 12-19 versus over 19 years of age (78.8% vs. 21.2%, respectively; p < 0.05). Furthermore, 40.2% of mothers were exposed to insecticides and 39.8% to herbicides and/or fungicides before or during pregnancy. Only 15.4% of the mothers consumed folic acid during the first trimester of pregnancy. Conclusion: The incidence of congenital abnormalities of the CNS in newborns is a serious problem, perhaps associated with exposure of the mother to pesticides and a deficient intake of folic acid. Therefore, it is necessary to strengthen prenatal care and health literacy to help reduce the occurrence of these disorders.