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Abstract Background High birth weight (BW), 4000 g or larger, is an established risk factor for childhood leukemia. However, its association with central nervous system (CNS) tumor risk is yet unclear. The present study examined it, analyzing data obtained from a case-control study conducted among three states from the US. The association with childhood leukemia risk was also further examined. Methods In this study, a data set provided by the Comprehensive Epidemiologic Data Resource was analyzed with an official permission. The original case-control study was conducted to examine the association between paternal preconception exposure to ionizing radiation and childhood cancer risk. Cases with childhood cancer were mainly ascertained from local hospitals, and controls were selected, matched with birth year (1-year category), county of residence, sex, ethnicity and maternal age (+/−2 years). Since the ID numbers were unavailable, conventional logistic analyses were conducted adjusting for those matching variables except for the county of residence. In addition to those variables, gestational age, age at diagnosis and study sites as covariables were included in the logistic models. Results Analyzed subjects were 72 CNS tumor cases, 124 leukemia cases and 822 controls born from 1945 to 1989. The odds ratios (ORs) of CNS tumor risk for children with low BWs (4000 g) were 2.0 (95% confidence interval [CI]) = 0.7, 5.9) and 2.5 (95%CI = 1.2, 5.2)], respectively. When high-BW children were restricted to those who were large for gestational age (LGA), the OR for high-BW children remained similar (OR = 2.7; 95%CI = 1.1, 6.2). On the other hand, the ORs of leukemia risk for children with low and high BWs were 0.8 (95%CI = 0.2, 3.0) and 1.4 (95%CI = 0.7, 2.6), respectively. In the normal range of BW (2500–4000 g), higher BW was positively associated with CNS tumor risk (beta = 0.0011, p for trend = 0.012). However, the association with leukemia risk was not significant (beta = −0.0002, p for trend = 0.475). Conclusion High-BW and LGA children had an elevated childhood CNS tumor risk. In the normal BW range, the BW itself was positively related to CNS tumor risk. No significant association between BW and childhood leukemia risk was observed in this study.