Objectives: To examine and analyse the intervention effects of the Early Start Denver Model (ESDM) on children with autism spectrum disorder (ASD). Methods: This meta-analysis evaluated the effect sizes in four major domains of measurement (autism symptoms, language, cognition, and social communication). A total of 624 participants with ASD were included in 11 high-quality randomized controlled trial studies. Results: The results indicated that the ESDM intervention resulted in significant improvement with moderate effect sizes in the cognition (g = 0.28), autism symptoms (g = 0.27), and language (g = 0.29) domains. The effect sizes of autism symptoms and language were moderated by country (Western versus Asian countries). However, there were no significant effects observed for the social communication domain. Conclusion: The ESDM intervention significantly improved autism symptoms, language, and cognition. The effect sizes of autism symptoms and language were larger in Asian countries than in Western countries.