Purpose Both air pollutant exposure and neonatal jaundice (NJ) have known effects on childhood asthma, but a higher total serum bilirubin (TSB) level has been associated with lung protection. This study aimed to assess whether prenatal/postnatal exposure to ambient air pollutants is related to the development of asthma in infants with NJ. Patients and Methods A nested case–control retrospective study was performed using the data of infants with NJ in the Kaohsiung Medical University Hospital Research Database. Data on average ambient air pollution concentrations within six months, the first year and second year after birth, and in the first, second and third prenatal trimesters were collected. NJ was defined as TSB levels ≥ 2 mg/dl with the diagnosis less than one-month-old. Asthma was defined as a diagnosis with medication use. We constructed conditional logistic regression models to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results Exposure to NO and SO 2 at all six time points in the study was significantly associated with an increased risk of preschool asthma in infants with NJ. The overall peak OR (95% CI) of SO 2 , PM 2.5 , PM 10 , NO, NO 2 , and NO X were 1.277 (1.129–1.444), 1.057 (1.023–1.092), 1.035 (1.011–1.059), 1.272 (1.111–1.455), 1.168 (1.083–1.259) and 1.104 (1.051–1.161), respectively. Fetuses in the first and second trimester were most vulnerable to ambient air pollutant exposure such as SO 2 PM 2.5 , NO, NO 2 and NO X during the prenatal period. Exposure to all six ambient air pollutants during the first and second years after birth significantly affected preschool asthma in NJ infants. Conclusion In different time windows, prenatal and postnatal exposure to SO 2 , PM 2.5 , PM 10 , NO, NO 2 , and NO X were associated with preschool asthma in NJ infants. The relatively high impact of NO and SO 2 exposure in infants with NJ requires further studies and prevention measures.