School burnout refers to psychological reactions to academic stress and loads and has been identified as a risk factor contributing to academic failure and subsequent mental health challenges. However, academic motivation, hope, and meaning in life can be potential combating factors against school burnout. This study aimed to examine the effects of academic motivation on school burnout in college students and explore mediator roles of hope and meaning in life. A path analysis was performed with the data collected from 544 Turkish college students to test the direct and indirect effects. The results showed that the direct effects from the three academic motivation variables to school burnout variables were larger than the indirect effects. Both mediators played roles in the relations between amotivation and efficacy and intrinsic motivation and efficacy. The last finding was that hope played more significant mediator roles than meaning in life. The results were discussed, along with implications for faculty, college counselors, and future studies.