Significance Several forms of the oxytocin neurohormone have been found in New World monkeys (NWMs). Previous research has suggested an association between these forms and behaviors typical of this primate branch, including paternal care and monogamy. Our study provides genetic, pharmacological, behavioral, and in silico evidence supporting this connection. Rats treated intranasally with two NWM oxytocin variants showed an increase in some parental care behaviors. The same two variants were found to elicit different cell-signaling profiles in cell-based assays compared with ancestral oxytocin. Our findings highlight how mutations in the OXT DNA sequence coding for a nonapeptide result in distinct signaling profiles that may be linked to the emergence of novel adaptive traits, in this case, paternal care and monogamy.