Fathering plays an important role in infants' socioemotional and cognitive development. Previous studies have identified brain regions that are important for parenting behavior in human mothers. However, the neural basis of parenting in human fathers is largely unexplored. In the current longitudinal study, we investigated structural changes in fathers' brains during the first 4 months postpartum using voxel-based morphometry analysis. Biological fathers (n = 16) with full-term, healthy infants were scanned at 2-4 weeks postpartum (time 1) and at 12-16 weeks postpartum (time 2). Fathers exhibited increase in gray matter (GM) volume in several neural regions involved in parental motivation, including the hypothalamus, amygdala, striatum, and lateral prefrontal cortex. On the other hand, fathers exhibited decreases in GM volume in the orbitofrontal cortex, posterior cingulate cortex, and insula. The findings provide evidence for neural plasticity in fathers' brains. We also discuss the distinct patterns of associations among neural changes, postpartum mood symptoms, and parenting behaviors among fathers.