The formation of new social interactions is vital for social animals, but the underlying neural mechanisms remain poorly understood. We identified CeANpbwr1 neurons, a population in central amygdala expressing neuropeptide B/W receptor-1 (NPBWR1), that play a critical role in these interactions. CeANpbwr1 neurons were activated during encounters with unfamiliar, but not with familiar, mice. Manipulations of CeANpbwr1 neurons showed that their excitation is essential for maintaining physical interactions with novel conspecifics. Activation of CeANpbwr1 neurons alleviated social deficits induced by chronic social defeat stress, suggesting therapeutic potential. Conversely, overexpression of human NPBWR1 in CeANpbwr1 neurons reduced activity of these neurons and impaired social interactions with unfamiliar mice. This effect was absent in a polymorphic variant of the human NPBWR1 gene (404A>T). These findings highlight how CeANpbwr1 neurons promote social novelty seeking and reveal a complex interplay between NPBWR1 genetic variations and social behavior.