Neighborhoods provide resources that may affect children’s achievement or moderate the influences of other developmental contexts, such as early care and education (ECE). Using a sample (N ≈ 12,430) from the 2010–2011 Early Childhood Longitudinal Study-Kindergarten Cohort, merged with census tract-level poverty data from the 2008–2012 American Community Survey, this article examines associations between center-based ECE participation, neighborhood poverty, and children’s academic skills and behavior at kindergarten entry. Findings suggest that children who attend center-based care in the year prior to kindergarten show higher math and reading scores across neighborhood contexts. Results provide limited evidence that neighborhood poverty moderates the associations between either Head Start or other types of center-based ECE participation and children’s outcomes at kindergarten, with children in moderate-high poverty neighborhoods showing stronger positive associations between who participated in Head Start or center care participation and math and reading scores, respectively, compared to those participating in low-poverty neighborhoods. Research and policy implications are discussed.