Existing literature points to the possibility that cortisol could be one link between maternal adversity and poorer parenting quality, but most studies have examined salivary cortisol concentrations rather than hair cortisol concentrations. The current study examined hair cortisol concentration (HCC) during the third trimester of pregnancy as a mediator between maternal adversity indicators (childhood abuse, severe mental illness, symptomatic functioning) and maternal caregiving behavior at 4 months postpartum. Forty-four women participated in the study: 30 with severe mental disorders, and 14 nonclinical controls. HCC was assessed during the third trimester of pregnancy (HCC-P) and at 4 months postpartum (HCC-4M). Sexual, physical, and emotional abuse were assessed by the Adverse Childhood Experiences Study Questionnaire. Maternal disrupted interaction was reliably coded from mother–infant video interactions during a Still-Face Procedure. Mediation models indicated that maternal HCC-P and HCC-4M mediated associations between maternal psychopathology (severe mental illness, symptomatic functioning) and maternal disrupted interaction at 4 months. Maternal HCC at 4 months also mediated associations between experienced childhood abuse and overall disrupted interaction. Our findings indicate that HCC may be a potential early biomarker for future caregiving challenges among mothers with severe mental illness and histories of childhood abuse.