Social insects offer powerful models to investigate the link between epigenetic regulation of genes and behavior because distinct tasks are segregated among nearly genetically identical females. Workers of the leafcutter ant genus Atta exhibit an extreme example of this task partitioning, wherein behaviors are typically segregated among highly phenotypically distinct individual types, or “castes”. Despite this extraordinary specialization, little is known about the molecular regulation of the behavioral castes in leafcutter ants. Here, we identify specific neuropeptides as mediators of caste division of labor in Atta cephalotes. We manipulate two of these neuropeptides to reprogram behavior of the Major defensive caste. We found high levels of the neuropeptide CCAP specifically in the leaf cutter caste—the signature behavioral type of the species. Here, injection of CCAP peptide into Major brain resulted in acquisition of leaf movement behavior and transcriptomic shift towards the leaf cutter. In a second finding, we investigated neuroparsin-A (NPA) in brood caretaking behavior. NPA showed elevated expression in the Major/Media (defensive/forager) castes relative to the Minor (caretaking) caste. RNAi-mediated reduction of NPA in the Major or Media brain resulted in acquisition of caretaking behavior and transcriptomic shift to caretaker Minor-like state. In contrast, injection of NPA peptide into the Minor brain suppressed caretaking behavior. Further, we compared the A. cephalotes transcriptome with that of a eusocial mammal (Naked Mole Rat), revealing global similarities of specific gene expression between foraging and caretaking castes. Moreover, despite the lack of a natural receptor in the mammalian system, our results show that NPA peptide can alter gene expression in Naked mole-rat cells similar to leaf cutter and indicate that NPA can re-purpose existing machinery in the eusocial mammal via tapping into insulin signaling. We propose that NPA governs caretaking behavior in leafcutter ants by controlling evolutionarily conserved mechanisms of behavioral regulation shared between insects and mammals, and underscore that neuropeptides dictate and can reprogram broad behavioral patterns in ants.