Brain, oxytocin, and parenting behavior were measured in primary-caregiving mothers, secondary-caregiving fathers, and primary-caregiving homosexual fathers raising infants without maternal involvement. Parenting integrated functioning of two neural networks: subcortical-paralimbic structures implicated in emotional processing and cortical circuits involved in social understanding. Mothers showed greater activation in the emotional processing network and fathers in the socio-cognitive circuits, which were differentially linked with oxytocin and behavior. Primary-caregiving fathers exhibited high amygdala activation similar to mothers, alongside high superior temporal sulcus (STS) activation comparable to fathers, and functional connectivity between amygdala and STS. Among all fathers, time spent in childcare correlated with amygdala-STS connectivity. Findings describe mechanisms of brain malleability with caregiving experiences in human fathers.