Background: A systematic literature review and meta-analysis was conducted to summarize the prevalence of KRAS, NRAS, and BRAF mutations in mCRC patients. These mutations have substantial implications for treatment decisions among mCRC patients. Methods: Multiple databases were searched to identify observational studies and clinical trials (standard of care arms only) that reported mutation status among mCRC patients. Random effects meta-analysis models were used to estimate summary prevalence estimates for each of the mutations. Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity in mutation prevalence. Results: The meta-analyses included 275 studies comprising over 77,000 mCRC patients. The summary prevalence estimate was 35.9% for KRAS mutations, 7.1% for BRAF mutations, and 4.1% for NRAS mutations. Female patients had significantly more KRAS and BRAF mutations than males (KRAS: 42.2% vs. 37.3%, p = 0.011; BRAF: 11.0% vs. 7.9%, p = 0.018), and significant variation by study location was observed for both KRAS (p = 0.025) and BRAF (p = 0.002) mutation prevalence. Conclusions: The prevalence of KRAS, BRAF, or NRAS mutations in mCRC patients varies significantly by gender and study location. compared to patients with wild-type tumors. The results of these analyses are informative for clinicians, patients, and researchers.