Background: Attachment-based parenting interventions have shown positive effects on early cortisol regulation, a key biomarker. Evaluations to date have focused on diurnal cortisol production in high-risk infants. It is important to understand whether attachment-based intervention may also improve stress-induced cortisol production in typically developing infants. This randomized controlled trial tested an enhanced model of U.S. Early Head Start (EHS) services that combined home-based EHS with a brief, attachment-based parenting intervention, Attachment and Biobehavioral Catch-up (ABC). The trial included 153 low-income mothers and their infants (M age 12.4 months [SD = 4.1]). Control participants received home-based EHS plus 10 weekly books. Intent-to-treat analyses using multilevel models revealed a significant indirect intervention effect on infants’ rates of cortisol change in response to a series of mild stressors. The intervention increased maternal sensitivity, which in turn improved cortisol regulation, particularly infants’ rates of cortisol recovery. The findings illustrate the efficacy of EHS plus ABC for supporting infants’ stress-induced cortisol regulation and implicate sensitive maternal behavior as the underlying driver of the intervention effect. Findings are discussed in terms of the preventative value of attachment-based parenting interventions that improve both parenting and infants’ physiological regulation.