We aimed to estimate the effects of overweight and obesity on carpal tunnel syndrome (CTS), and to assess whether sex modifies the associations. Literature searches were conducted in PubMed, Embase, Web of Science, Scopus, Google Scholar and ResearchGate databases from 1953 to February 2015. Fifty-eight studies consisting of 1,379,372 individuals qualified for a meta-analysis. We used a random-effects meta-analysis, assessed heterogeneity and publication bias, and performed sensitivity analyses. Overweight increased the risk of CTS or carpal tunnel release 1.5-fold (pooled confounder-adjusted odds ratio [OR] = 1.47, 95% CI 1.37–1.57, N = 1,279,546) and obesity twofold (adjusted OR = 2.02, 95% CI 1.92–2.13, N = 1,362,207). Each one-unit increase in body mass index increased the risk of CTS by 7.4% (adjusted OR = 1.074, 95% CI 1.071–1.077, N = 1,258,578). Overweight and obesity had stronger effects on carpal tunnel release than CTS. The associations did not differ between men and women, and they were independent of study design. Moreover, the associations were not due to bias or confounding. Excess body mass markedly increases the risk of CTS. As the prevalence of overweight and obesity is increasing globally, overweight-related CTS is expected to increase. Future studies should investigate whether a square-shaped wrist and exposure to physical workload factors potentiate the adverse effect of obesity on the median nerve.