Agreeable people are more likely to display prosocial attitudes and helpful behavior in a broad range of situations. Here we show that this tendency interacts with the personal characteristics of interaction partners. In an online study (n = 284), participants were given the opportunity to report attitudes toward and make monetary donations to needy individuals who were described in dynamically generated biographies. Using a machine learning and multilevel modeling framework, we tested three potential explanations for the facilitatory influence of Agreeableness on charitable behavior. We find that Agreeableness preferentially increased donations and prosocial attitudes toward targets normatively rated as being more deserving. Our results advance understanding of person-by-situation interactions in the context of charitable behavior and prosocial attitudes.