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Altruism is an evolutionarily conserved neurobehavioral mechanism for responding to others’ needs, even at a cost to the self. It is thought to be rooted in offspring care and is most prominent in kin and close relationships, but also extends to others. We investigated the neural and genetic (OXTR rs53576 and AVPR1a rs3) correlates of altruism (with the Agape scale) in newlywed pair-bonds. Using functional MRI, 18 participants were scanned (T1) while viewing happy or sad face images of the partner; of a stranger; or of a highly familiar, neutral acquaintance (HFN). Thirteen returned for another scan 11 months later (T2), and the additional control of a neutral expression of the partner and stranger was added. At both time points, the right ventral pallidum (VP), ventral tegmental area, and caudate showed significant responses to Partner (romantic) versus HFN images. At T2, altruism scores, OXTR rs53576 G alleles, and AVPR1a rs3 long alleles showed positive correlations with activity in the left VP/accumbens, amygdala, and septum for both Happy and Sad Partner expressions compared to neutral expressions, but not for strangers. However, when the Happy or Sad partner was compared to a Happy or Sad stranger, positive correlations were limited mainly to the amygdala/entorhinal cortex region. This study localized neural correlates of altruism in pair-bonds, including the VP and the amygdala. Also, responsivity in the VP showed increases or decreases as a function of OXTR and AVPR1a variants. These variations may contribute to behavioral heterogeneity and diverse strategies observed in complex social behaviors. In conclusion, the neural and hormonal basis of altruism in pair-bonds may be phylogenetically conserved, yet genetically variable, and promote pair-bond stability and enhance survival and cooperation of the species.