Hypertension and overweight are growing public health concerns in school-aged children. We examined whether cardiorespiratory fitness and sport participation contribute to the prevention of hypertension and overweight. We conducted a cluster-randomized controlled trial with 853 children aged 8–13 years in eight primary schools in Port Elizabeth, South Africa. Cardiorespiratory fitness, sport participation, body mass index, and blood pressure were assessed at baseline and after a physical activity intervention, which took place at two time-points (July–September 2015 and February–April 2016) for 10 weeks each. Mixed logistic regressions were employed to analyze the data. At baseline, 18.8% of the children were classified as overweight/obese and 13.5% as hypertensive. High cardiorespiratory fitness and high sport participation were negatively associated with overweight/obesity, while high sport participation was associated with lower risk for hypertension. Longitudinally, normal weight children who initially had higher cardiorespiratory fitness showed less decrease in this variable, while those who participated in the physical activity intervention were less likely to become overweight/obese. High cardiorespiratory fitness and sport participation are linked with children’s weight status. Children who are fit and participate regularly in sport outside school hours are less likely to be hypertensive. Our findings highlight the importance of regular extracurricular physical activity and maintaining cardiorespiratory fitness levels.