Background: The purpose of the study was to examine the associations among cardiorespiratory fitness (CRF), weight status and academic achievement in youth, and to determine if these relationships are moderated by poverty status. Methods: The sample included 5th (N = 27,791) and 8th grade (N = 16,047) South Carolina students. Academic achievement was assessed using a state-wide assessment and classified into 2 categories (ie, does not meet/approaches standards vs meets/exceeds standards). CRF was assessed and expressed as Healthy Fitness Zone (HFZ) or Needs Improvement/Needs-Improvement-Health Risk. Students' demographics and poverty status were reported. Multilevel logistic regression analyses were used to examine the association between CRF, weight status and academic achievement. Interaction terms were introduced into the final models. Analyses were performed separately by grade level and academic subject. Results: The CRF was significantly associated with the odds of meeting/exceeding academic standards after controlling for covariates and adjusting for weight status. The relationship between CRF and academic achievement varied significantly by poverty status. After adjustment for CRF, weight status was not significantly associated with academic achievement. Conclusions: The odds of achieving academic standards were significantly higher among students achieving CRF HFZ regardless of poverty status. CRF may partially mitigate the adverse effect of poverty on academic achievement.