Background: Cardiorespiratory fitness (CRF) plays a significant role in health and academic performance in youth. The purpose of this study was to examine the longitudinal relationship between CRF and academic performance from fifth to eighth grade among a large, diverse, and state-wide cohort of students, and to determine the extent to which the relationship between change in CRF and academic performance is moderated by poverty status. Methods: CRF and academic performance data were obtained for a retrospective state-wide cohort of 11,013 students with baseline (fifth grade, school year 2015-2016) and follow-up (eighth grade, school year 2018-2019) data. Analysis of covariance was used to examine the association between changes in CRF over a 3-year follow-up period and eighth grade academic performance. Results: After adjusting for covariates, change in CRF and poverty status were positively and significantly associated with eighth grade academic performance. Poverty status did not significantly moderate the association between changes in CRF and academic performance. Conclusions: Schools should prioritize evidence-based policies and programs that optimize students' access to high quantity and quality physical activity throughout the school day. Such efforts can improve and maintain student CRF and thus academic performance outcomes.