Background. Limited data suggest air pollution exposures may contribute to pediatric high blood pressure (HBP), a known predictor of adult cardiovascular diseases. Methods. We investigated this association in the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, a sociodemographically diverse pregnancy cohort in the southern United States with participants enrolled from 2006 to 2011. We included 822 mother-child dyads with available address histories and a valid child blood pressure measurement at 4-6 y. Systolic (SBP) and diastolic blood pressures (DBP) were converted to age-, sex-, and height-specific percentiles for normal-weight U.S. Children. HBP was classified based on SBP or DBP ≥90th percentile. Nitrogen dioxide (NO2) and particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5) estimates in both pre- and postnatal windows were obtained from annual national models and spatiotemporal models, respectively. We fit multivariate Linear and Poisson regressions and explored multiplicative joint effects with maternal nutrition, child sex, and maternal race using interaction terms. Results. Mean PM2.5 and NO2 in the prenatal period were 10.8 [standard deviation (SD): 0.9] μg/m3 and 10.0 (SD:2.4) ppb, respectively, and 9.9 (SD:0.6) μg/m3 and 8.8 (SD: 1.9) ppb from birth to the 4-y-old birthday. On average, SBP percentile increased by 14.6 (95% CI: 4.6, 24.6), and DBP percentile increased by 8.7 (95% CI: 1.4, 15.9) with each 2-μg/m3 increase in second-trimester PM2.5. PM2.5 averaged over the prenatal period was only significantly associated with higher DBP percentiles [β = 11.6 (95% CI: 2.9, 20.2)]. Positive associations of second-trimester PM2.5 with SBP and DBP percentiles were stronger in children with maternal folate concentrations in the lowest quartile (pinteraction = 0.05 and 0.07, respectively) and associations with DBP percentiles were stronger in female children (pinteraction = 0.05). We did not detect significant association of NO2, road proximity, and postnatal PM2.5 with any outcomes. Conclusions. The findings suggest that higher prenatal PM2.5 exposure, particularly in the second trimester, is associated with elevated early childhood blood pressure. This adverse association could be modified by pregnancy folate concentrations.