The current investigation aimed to investigate the longitudinal association between physical fitness and academic performance over 3 years in adolescents. A secondary aim was to determine to what extent waist circumference mediated the association between physical fitness and academic performance. For the current study, 1020 students from first grade [mean age: 7.87 (0.34) y] to fifth grade [mean age: 11.87 (0.37) y] were monitored annually for 3 years (2010-2013). Physical fitness was assessed using the Andersen test, 5 × 5-m shuttle run, jump height, and grip strength tests and by constructing a composite score combining all 4 fitness tests. Academic performance was assessed by national standardized tests in Danish language and math. Generalized structural equation modeling was used to evaluate the relationships between these variables. The Andersen test (standardized β = 0.15 SD), shuttle run (β = -0.18 SD), jump height (β = 0.10 SD), and the fitness composite score (β = 0.23 SD) were positively associated with academic performance over 3years. In addition, waist circumference partially mediated the association between physical fitness and academic performance. Thus, physical fitness abilities should be stimulated during childhood and early adolescence because of their positive association with academic performance.