Background: Prenatal stress negatively affects fetal development, which in turn may affect infant hypothalamic-pituitary adrenal (HPA) axis regulation and behavioral functioning. We examined effects of exposure to a traumatic stressor in families [intimate partner violence (IPV)] on both infants’ HPA axis reactivity to stress and their internalizing and externalizing behaviors. Structural equation modeling revealed that prenatal, but not postnatal, IPV was independently associated with infant cortisol reactivity and problem behavior. Maternal mental health predicted infant behavioral functioning but not infant HPA axis reactivity. These findings are consistent with the prenatal programming hypothesis; that is, early life stress affects later risk and vulnerability for altered physiological and behavioral regulation.