Objectives The aim of the present study was to evaluate the relationship between the rs9939609 fat mass and obesity‐associated (FTO) polymorphism and cardiorespiratory fitness (CRF) with overweight/obesity outcomes in youth. Methods This study included 420 youths, comprising 211 boys and 209 girls aged 7–17. Overweight/obesity were evaluated by body mass index (BMI), waist circumference (WC), and the percentage of fat (PF) according to two skinfold thickness measurements. Genotyping of the rs9939609 polymorphism was conducted using real‐time Polymerase Chain Reaction (PCR) utilizing TaqMan® probes, and CRF was evaluated through a 9‐minute run/walk test, categorized as fit or unfit. Logistic regression was utilized to evaluate a possible association between the polymorphism and CRF, with three obesity indicators evaluated. Results Individuals with the genotype risk (AA) of FTO polymorphism rs9939609 showed higher prevalence of overweight/obesity, as evaluated by BMI (OR: 3.21; CI: 1.71–6.05), WC (OR: 2.59; CI: 1.35–4.97), and PF (OR: 2.59; CI: 1.36–4.92). Additionally, students with the AA genotype in the unfit model had a significant odds ratio for obesity (OR: 4.40; CI: 1.83–10.61 for BMI; OR: 3.54; CI: 1.58–7.96 for WC), whereas we did not observe associations between the AA genotype with BMI and WC using the fit model. Conversely, PF was associated with the AA genotype only in the fit model (OR: 3.24; CI: 1.26–8.34). Conclusions This study demonstrated that the rs9939609 (FTO) polymorphism showed a relationship with obesity in the population studied and an interaction with CRF. Students with low levels of CRF and the AA genotype have a higher risk of being overweight/obese. This association was not found in students with higher levels of CRF. Am. J. Hum. Biol. 28:381–386, 2016. © 2015 Wiley Periodicals, Inc.