Humans often sacrifice material benefits to endorse or to oppose societal causes based on moral beliefs. Charitable donation behavior, which has been the target of recent experimental economics studies, is an outstanding contemporary manifestation of this ability. Yet the neural bases of this unique aspect of human altruism, which extends beyond interpersonal interactions, remain obscure. In this article, we use functional magnetic resonance imaging while participants anonymously donated to or opposed real charitable organizations related to major societal causes. We show that the mesolimbic reward system is engaged by donations in the same way as when monetary rewards are obtained. Furthermore, medial orbitofrontal-subgenual and lateral orbitofrontal areas, which also play key roles in more primitive mechanisms of social attachment and aversion, specifically mediate decisions to donate or to oppose societal causes. Remarkably, more anterior sectors of the prefrontal cortex are distinctively recruited when altruistic choices prevail over selfish material interests.