Background No prior study has examined associations between prenatal and early-life stress on childhood lung function or identified critical windows of exposure. Objective To prospectively examine associations between prenatal and early-life stress and childhood lung function. Methods Stress was indexed by a maternal negative life events (NLEs) score ascertained during pregnancy and between 1 and 2 years post partum. Spirometry was performed when children were a mean (SD) of 6.99 (0.89) years old. Associations of prenatal and early postnatal stress with spirometry z scores were examined in 199 children using linear regression. Effect modification by child sex was explored. Results Most mothers were minorities (65% Hispanic, 21% African American), had 12 years or less of education (67%), and did not smoke prenatally (78%). The highest level of prenatal stress (≥5 NLEs) was associated with lower levels of forced expiratory volume in 1 second (FEV1) (z score = −0.53, P = .03), forced vital capacity (FVC) (z score = −0.49, P = .04), and forced expiratory flow between 25% and 75% (FEF25%–75%) (z score = −0.68, P = .01) after covariate adjustment; effects were similar for postnatal stress considered separately. In sex-stratified analyses, high postnatal stress (≥5 NLEs) was associated with lower FEV1 (z score = −0.76, P = .01), FVC (z score = −0.77, P = .01), and FEF25%–75% (z score = −0.67, P = .02) in boys but not girls, although the interaction term was not significant (P for interaction >.10). Conclusion These are the first prospective data that link perinatal stress with reduced child lung function. High levels of stress in the prenatal and postnatal periods were associated with symmetric reductions in FEV1 and FVC consistent with impaired lung growth. Given that lung function growth patterns are established by 7 years of age, these findings have lifelong implications.