Humans often make sacrifices for societal causes based on moral beliefs. Charitable donation behavior, studied in experimental economics, reflects this ability. The neural basis of altruism beyond interpersonal interactions remains unclear. This study used fMRI to examine donations to or opposition of real charitable organizations linked to societal causes. The mesolimbic reward system was activated by donations, similar to monetary rewards. Medial and lateral orbitofrontal areas mediated decisions to donate or oppose causes, while anterior prefrontal regions were engaged when altruistic choices outweighed self-interest. Participants consistently made costly decisions, sacrificing an average of 40% of their endowment. Altruistic decisions involved longer response times and higher compassion scores for donated causes and higher anger scores for opposed causes. The midbrain ventral tegmental area, dorsal and ventral striatum were activated by both monetary rewards and donations. The subgenual area was specifically activated by donations, playing a key role in social attachment and affiliative reward. The lateral orbitofrontal cortex was activated by opposition decisions, indicating its role in social aversion. Costly decisions involved activation of the anterior prefrontal cortex, including the frontopolar cortex and medial frontal gyrus, and were associated with longer response times. The dorsal anterior cingulate cortex was correlated with response times, reflecting its role in conflict and error monitoring. Anterior prefrontal cortex activity to costly donations was highly correlated with self-reported engagement in real-life charitable activities. These findings suggest that human altruism involves distinct neural systems: the mesolimbic reward system provides general reinforcement, the subgenual area and lateral orbitofrontal cortex mediate social attachment and aversion, and the anterior prefrontal cortex is crucial for complex reinforcement contingencies related to altruistic decisions. The study highlights the role of fronto-limbic networks in human altruism, linking motivational value to abstract moral beliefs and societal causes.Humans often make sacrifices for societal causes based on moral beliefs. Charitable donation behavior, studied in experimental economics, reflects this ability. The neural basis of altruism beyond interpersonal interactions remains unclear. This study used fMRI to examine donations to or opposition of real charitable organizations linked to societal causes. The mesolimbic reward system was activated by donations, similar to monetary rewards. Medial and lateral orbitofrontal areas mediated decisions to donate or oppose causes, while anterior prefrontal regions were engaged when altruistic choices outweighed self-interest. Participants consistently made costly decisions, sacrificing an average of 40% of their endowment. Altruistic decisions involved longer response times and higher compassion scores for donated causes and higher anger scores for opposed causes. The midbrain ventral tegmental area, dorsal and ventral striatum were activated by both monetary rewards and donations. The subgenual area was specifically activated by donations, playing a key role in social attachment and affiliative reward. The lateral orbitofrontal cortex was activated by opposition decisions, indicating its role in social aversion. Costly decisions involved activation of the anterior prefrontal cortex, including the frontopolar cortex and medial frontal gyrus, and were associated with longer response times. The dorsal anterior cingulate cortex was correlated with response times, reflecting its role in conflict and error monitoring. Anterior prefrontal cortex activity to costly donations was highly correlated with self-reported engagement in real-life charitable activities. These findings suggest that human altruism involves distinct neural systems: the mesolimbic reward system provides general reinforcement, the subgenual area and lateral orbitofrontal cortex mediate social attachment and aversion, and the anterior prefrontal cortex is crucial for complex reinforcement contingencies related to altruistic decisions. The study highlights the role of fronto-limbic networks in human altruism, linking motivational value to abstract moral beliefs and societal causes.