Racism, segregation, and inequality contribute to health outcomes and drive health disparities across the life course, including for newborn infants and their families. In this review, we address their effects on the health and well-being of newborn infants and their families with a focus on preterm birth. We discuss three causal pathways: increased risk; lower-quality care; and socioeconomic disadvantages that persist into infancy, childhood, and beyond. For each pathway, we propose specific interventions and research priorities that may remedy the adverse effects of racism, segregation, and inequality. Infants and their families will not realize the full benefit of advances in perinatal and neonatal care until we, collectively, accept our responsibility for addressing the range of determinants that shape long-term outcomes.