Parental care is essential for the survival of mammals, yet the mechanisms underlying its evolution remain largely unknown. I found that two sister species of mice, Peromyscus polionotus and Peromyscus maniculatus, have large and heritable (genetically based) differences in parental behavior. Using quantitative genetics, I identified 12 genomic regions that affect parental care, 8 of which have sex-specific effects, suggesting that parental care can evolve independently in males and females. Furthermore, some regions affect parental care broadly, whereas others affect specific behaviors, such as nest building. Of the genes linked to differences in nest-building behavior, vasopressin is differentially expressed in the hypothalamus (a brain region critical for parental care) of the two species, with increased levels associated with less nest building. Using pharmacology in Peromyscus and manipulation of neuronal activity in laboratory Mus mice, I found that vasopressin inhibits nest building but not other parental behaviours. Together, these results indicate that variation in the ancient neuropeptide vasopressin (present since early in animal evolution) contributes to interspecific differences in parental care.