Adverse childhood experiences (ACEs) are common risk factors for unhealthy behaviors and poor health outcomes throughout the life course, but their relationship with prenatal substance use is understudied. This retrospective cohort study included 44,284 patients with pregnancies between January 1, 2022, and June 28, 2024, in a large healthcare system in Northern California, United States of America with universal screening for ACEs, resilience, and substance use during early pregnancy.