One of the main challenges in intervention research today is understanding who benefits from universal school programs. Partly, this challenge involves capturing the diversity of experiences, needs, and traits in across students that may explain “who benefits” from interventions. Here, we studied motivation profiles (i.e., systems of beliefs, goals, and behaviors) to understand variation in treatment effects of social and emotional school interventions. Using data from a large intervention study (2,097 schools), we found four motivation profiles (growth, multiple goals, disconnected, and severely disconnected). Moreover, we found differential effects of a short social and emotional intervention, such that growth and severely disconnected, but not multiple goals or disconnected, students increased their test scores. In addition, each profile increased their use of a unique set of learning strategies. These findings suggest that motivation profiles can expand what we know about “who benefits” from social and emotional interventions and generate insights on how to improve interventions to reach a wider range of students.