Self-transcendence refers to a shift in mindset from focusing on self-interests to the well-being of others. We offer an integrative neural model of self-transcendence in the context of persuasive messaging by examining the mechanisms of self-transcendence in promoting receptivity to health messages and behavior change. Specifically, we posited that focusing on values and activities that transcend the self can allow people to see that their self-worth is not tied to a specific behavior in question, and in turn become more receptive to subsequent, otherwise threatening health information. To test whether inducing self-transcendent mindsets before message delivery would help overcome defensiveness and increase receptivity, we used two priming tasks, affirmation and compassion, to elicit a transcendent mindset among 220 sedentary adults. As preregistered, those who completed a self-transcendence task before health message exposure, compared with controls, showed greater increases in objectively logged levels of physical activity throughout the following month. In the brain, self-transcendence tasks up-regulated activity in a region of the ventromedial prefrontal cortex, chosen for its role in positive valuation and reward processing. During subsequent health message exposure, self-transcendence priming was associated with increased activity in subregions of the ventromedial prefrontal cortex, implicated in self-related processing and positive valuation, which predicted later decreases in sedentary behavior. The present findings suggest that having a positive self-transcendent mindset can increase behavior change, in part by increasing neural receptivity to health messaging.