This longitudinal study of low-income families tested neighborhood-, family-, and child-centered promotive factors in early childhood, responses to an early family intervention, and their interactions as predictors of school-entry levels of and early school-age gains in academic skills. Using a racially-diverse, low-income sample (n = 527) from a randomized controlled trial of the Family Check-Up (FCU) intervention and Bayesian multilevel regression modeling, we tested whether neighborhood cohesion, positive mother–child engagement, and child self-regulation in early childhood (ages 2–5 years) and their interactions with FCU group assignment predicted the intercept and slope of academic skills across child age 5, 7.5, and 8.5 years. Higher positive mother–child engagement and child self-regulation predicted higher academic skills at school entry. An interaction between the FCU intervention and positive mother–child engagement predicted gains in academic skills compared to national norms. The findings suggest the FCU intervention leveraged positive mother–child engagement in early childhood to promote academic skills, offering a potential avenue from which to prevent income achievement gaps before school entry.