Background Children of maltreated mothers are at increased risk for adverse physical and psychological health. Both prenatal and postnatal alterations in offspring biological stress systems have been proposed as mechanisms contributing to such transmission. The aim of the current study was to assess whether maternal postnatal care of the infant moderated any effect of maternal childhood maltreatment on infant cortisol output during a mild stressor at 4 months of age. Methods Participants included 181 mother–infant dyads, screened at recruitment to result in 57.4% reporting one or more forms of childhood maltreatment. Mothers were assessed for quality of caregiving, and infants were assessed for infant salivary cortisol output during the Still‐Face Paradigm at infant age 4 months. Maternal childhood maltreatment was assessed using the Maltreatment and Abuse Chronology of Exposure (MACE) self‐report scales. Results Greater severity of maternal childhood neglect interacted with higher levels of maternal disoriented caregiving to predict higher infant cortisol output over the course of the Still‐Face Paradigm. In contrast, maternal childhood abuse interacted with higher levels of maternal negative‐intrusion to predict lower infant cortisol output. Greater maternal role confusion was linked to greater infant cortisol output regardless of maternal maltreatment history. Conclusions Maternal caregiving may moderate the effects of risk factors existing prior to the infant's birth. Disoriented caregiving in the context of maternal childhood neglect and negative‐intrusive behavior in the context of maternal childhood abuse were associated with opposite directions of effect on infant stress hormone output. The results suggest that interventions addressing risks from both prenatal and postnatal periods may be most effective in mitigating intergenerational effects of maltreatment.