The health and well-being of childbearing women and children in the US should set a world standard. However, women and children in the US experience higher rates of morbidity and mortality than women and children in almost all other industrialized countries, with marked racial and ethnic disparities. The unfolding effects of the coronavirus disease 2019 (COVID-19) pandemic have highlighted such disparities. In this article, which is part of the National Academy of Medicine’s Vital Directions for Health and Health Care: Priorities for 2021 initiative, we draw on a life-course framework to highlight promising interventions and recommend key improvements in programs and policies to optimize health and well-being among women and children in the US. The recommendations address ensuring access, transforming health care, and addressing social and environmental determinants.