Abstract Purpose The effects of general anesthesia on neurodevelopment in children remain controversial. We explored the relationship between general anesthesia and neurodevelopment in children participating in the Japan Environment and Children’s Study (JECS). Methods This study enrolled children born between 37 and 41 weeks of pregnancy via single-vaginal delivery to pregnant women registered in the JECS between January 2011 and March 2014. Data were collected from mother-completed questionnaires and medical transcripts. Neurodevelopment in five domains was assessed every 6 months between 12 and 48 months of age, using the Ages and Stages Questionnaires. The associations between general anesthesia exposure during early childhood and neurodevelopment in children were evaluated at each time point. Adjusted odds ratios and 95% confidence intervals were estimated after covariate adjustment using logistic regression models. Results Children who received general anesthesia before age 1 year had higher risks of neurodevelopmental delay in all five domains throughout the observational period. The largest risk was for gross motor delay at 18 months (adjusted odds ratio: 3.51; 95% confidence interval: 2.75–4.49). The effects on the incidence of neurodevelopmental delays after age 3 were not observed except for problem solving at 48 months. The risk of neurodevelopmental delay in children who first received general anesthesia after age 1 was considerably small. Conclusions This study suggests that general anesthesia administration before age 1 is associated with neurodevelopmental delay during 1–4 years of age. The risk of general anesthesia after age 1 may be small.