Despite consensus that physical fitness (PF) plays an important role in promoting mental health and academic achievement, little is known regarding the mechanisms by which this effect works. Blair, Cheng, and Holder (2001) proposed a conceptual model to identify the behavioral mechanism of health outcomes, in which both health-related PF and skill-related PF were identified as the direct determinants of health outcomes. Guided by Blair and colleagues' model, the primary purpose of this study was to examine the association between health-related PF, skill-related PF, depression and academic achievement among adolescents. The second purpose was to investigate whether depression would mediate the association between physical fitness and academic achievement among this population. A total of 144 adolescents (M age = 14.55, SD = 0.62) were recruited from two middle schools. Health-related PF was significantly associated with depression, and skill-related PF was related to academic achievement. Mediation analysis supports the statistically significant indirect effect of depression on the relation between health-related PF and academic achievement. The findings suggest that individuals who are physically fit and show positive mental functioning may have better academic achievement during adolescence.