Academic burnout seriously affects the academic performance and mental health of college students. This study developed a multi-mediation model to investigate the relationship between academic self-efficacy and academic burnout. A total of 1431 undergraduate students (51.85% female) were recruited to participate in this study. And we used SPSS PROCESS developed by Hayes to examine the mediating role of academic self-efficacy and academic burnout. The results indicated that academic self-efficacy can negatively predict academic burnout. Moreover, intrinsic motivation and learning engagement have a significant mediating effect between academic self-efficacy and academic burnout. Finally, we constructed a model comprising four variables and found that it explained 47.62% of the variance in academic burnout. These findings can be conducive to a suitable intervention path to reduce academic burnout of Chinese college students, so as to develop effective instructional strategies to improve their learning performance.