Background <p>Obesity is an important public health issue. Virtual reality provides an opportunity to increase benefits of traditional exercise programs with more immersive, interactive, and enjoyable experiences for weight control.</p> Objectives <p>This study aimed to explore the efficacy of virtual reality-enhanced exergames for obesity-related outcomes, including body weight, body mass index, body fat, and waist circumference.</p> Methods <p>Six electronic databases, including PubMed, Embase, Scopus, Web of Science, Medline, and CINAHL Plus, were searched for randomized controlled trials. A systematic review and meta-analysis were conducted using a random-effects model. In total, 12 qualified studies were selected for both qualitative and quantitative syntheses.</p> Results <p>Virtual reality-enhanced exergames exerted small significant effects on improving body weight, body mass index, and body fat percentage. Low heterogeneity and no significant publication bias were found among the studies.</p> Conclusions <p>Creating an immersive virtual world is an interesting and effective strategy for users to engage in physical activity. Virtual reality-enhanced exergames are recommended for weight control and obesity prevention across populations.</p>