Children with intellectual disability (ID) are more vulnerable to health conditions than their typically developing peers. Evidence of effective interventions is scarce. A randomized controlled trial was conducted in 30 overweight and obese children with intellectual disability (ID) in China to evaluate a 12-week school-based physical activity intervention for obesity, health-related physical fitness (HRPF), and blood pressure. The intervention consisted of 24 physical activity (PA) sessions (2 sessions/week, 60 min/session), with exercise intensity progressively increasing from a moderate level to a vigorous level. All participants were followed up for 12 weeks after the intervention period to evaluate sustained effects. Outcomes were repeatedly measured at baseline, after the intervention, and after follow-up. The intervention was effective in reducing some obesity-related outcomes (including weight and body mass index) and improving some HRPF-related outcomes (including the 6 min walk test and the 30 s sit-to-stand test), with the significant effects being sustained after the 12-week follow-up. No effect was observed on blood pressure. The findings of this study contribute to the development and implementation of PA interventions to reduce obesity and improve HRPF in children with ID.