In Western culture, romantic love is commonly a basis for marriage. Although it is associated with relationship satisfaction, stability, and individual well-being, many couples experience declines in romantic love. In newlyweds, specifically, changes in love predict marital outcomes. However, the biological mechanisms underlying the critical transition to marriage are unknown. Thus, for the first time, we explored the neural and genetic correlates of romantic love in newlyweds. Nineteen first-time newlyweds were scanned (with functional MRI) while viewing face images of the partner versus a familiar acquaintance, around the time of the wedding (T1) and 1 year after (T2). They also provided saliva samples for genetic analysis (AVPR1a rs3, OXTR rs53576, COMT rs4680, and DRD4-7R), and completed self-report measures of relationship quality including the Eros (romantic love) scale. We hypothesized that romantic love is a developed form of the mammalian drive to find, and keep, preferred mates; and that its maintenance is orchestrated by the brain’s reward system. Results showed that, at both time points, romantic love maintenance (Eros difference score: T2-T1) was associated with activation of the dopamine-rich substantia nigra in response to face images of the partner. Interactions with vasopressin, oxytocin, and dopamine genes implicated in pair-bonding (AVPR1a rs3, OXTR rs53576, COMT rs4680, and DRD4-7R) also conferred strong activation in the dopamine-rich ventral tegmental area at both time points. Consistent with work highlighting the role of sexual intimacy in relationships, romantic love maintenance showed correlations in the paracentral lobule (genital region) and cortical areas involved in sensory and cognitive processing (occipital, angular gyrus, insular cortex). These findings suggest that romantic love, and its maintenance, are orchestrated by dopamine-, vasopressin- and oxytocin-rich brain regions, as seen in humans and other monogamous animals. We also provide genetic evidence of polymorphisms associated with oxytocin, vasopressin and dopamine function that affect the propensity to sustain romantic love in early stage marriages. We conclude that romantic love maintenance is part of a broad mammalian strategy for reproduction and long-term attachment that is influenced by basic reward circuitry, complex cognitive processes, and genetic factors.