Epigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health. We sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes. We estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother-child pairs in Project Viva. We identified individual CpGs associated with residential-proximity-to-roadways at birth using robust linear regression Formula: see text. We also estimated association between proximity-to-roadways at birth and methylation of the same sites in blood samples collected at age 7-11 y (Formula: see text). We ran the same analyses in the Generation R Study for replication (Formula: see text). In Project Viva, we investigated associations of differential methylation at birth with midchildhood cognition using linear regression. Living closer to major roadways at birth was associated with higher cord blood (and-more weakly-midchildhood blood) methylation of four sites in LAMB2. For each halving of residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA methylation at cg05654765 95% confidence interval (CI): (0.54%, 1.10%), 0.88% at cg14099457 95% CI: (0.56%, 1.19%), 0.19% at cg03732535 95% CI: (0.11%, 0.28), and 1.08% at cg02954987 95% CI: (0.65%, 1.51%). Higher cord blood methylation of these sites was associated with lower midchildhood nonverbal cognitive scores. Our results did not replicate in the Generation R Study. Our discovery results must be interpreted with caution, given that they were not replicated in a separate cohort. However, living close to major roadways at birth was associated with cord blood methylation of sites in LAMB2-a gene known to be linked to axonal development-in our U.S. cohort. Higher methylation of these sites associated with lower nonverbal cognitive scores at age 7-11 y in the same children. https://doi.org/10.1289/EHP2034.