This study aimed to contribute to a holistic analysis of the effect of school burnout on academic achievement and well-being in high school students. For this purpose, a structural equation model made up of variables, including self-regulation, student-teacher relationships, peer relationships, family involvement to school, school burnout, academic achievement, and well-being, was tested. The sample of study consisted of 866 high school students from seven different types of high schools. The data of study were collected using a set of eight scales consisting of the Personal Information Form, Self-Regulation Scale, the Friendship Qualities Scale, the Self-Determination Theory-Based Student-Teacher Relationship Questionnaire-High School Form, the Perceived Parental and Teacher Academic Involvement Scale, the Maslach Burnout Inventory-Student Survey, the Academic Achievement (GPA), and the EPOCH Measure of Well-Being (EPOCH). Total six hypotheses were tested with the hypothetical model established within the scope of the study. As a result of the analysis, it was found that all of the hypotheses regarding the proposed hypothetical model were accepted, and the model was confirmed. The findings of the study revealed that each of the variables, namely, self-regulation, student-teacher relationships, peer relationships, and family involvement to school, had a direct and negative predictor effect on school burnout.