Childhood asthma, a growing health concern, has been associated with low birth weight and elevated body mass index. This study tested the hypothesis that overweight and obese adolescents with a history of low birth weight are at even greater risk of developing asthma. A cohort of 75,871 junior high school students was screened for asthma during 1995–1996 in Taiwan. Birth weight and estimated gestational age were obtained from the birth registry. Logistic regression and simple regression analyses were adjusted for confounding variables. Asthma was more prevalent in those with birth weights below 3,000 g and higher adolescent body mass indexes. Furthermore, those with both characteristics were consistently most likely to have asthma. Whether the asthma diagnosis among low-birth-weight subjects was assigned by physicians or medical questionnaire, the risks were elevated for both overweight (physician diagnosis: odds ratio = 1.41; medical questionnaire: odds ratio = 1.25) and obese (physician diagnosis: odds ratio = 1.38; medical questionnaire: odds ratio = 1.47) boys as well as overweight (physician diagnosis: odds ratio = 1.63; medical questionnaire: odds ratio = 1.30) and obese (physician diagnosis: odds ratio = 1.44; medical questionnaire: odds ratio = 1.32) girls (P < 0.05). Low birth weight predisposes one to develop asthma, and excess body mass amplifies the risk. A sex difference was observed. This study suggests that prenatal care and nutritional counseling could reduce asthma prevalence.