Whereas significant advances have been made in understanding how exposure to early adversity gets under the skin of children to result in long term changes in developmental outcomes, the processes by which positive social relationships become biologically embedded remain poorly understood. The aim of this study was to understand the pathways by which maternal and infant social environments become biologically embedded in infant cortisol reactivity. Two hundred seventy-two pregnant women and their infants were prospectively assessed during pregnancy and at 6 months postpartum. In serial mediation analyses, higher perceived social support from partners during pregnancy was associated with lower infant cortisol reactivity or larger decreases in cortisol in response to a stressor at 6 months of age via lower self-reported prenatal maternal depression and higher mother-infant interaction quality. The findings add to our understanding of how perinatal social relationships become biologically embedded in child development.