Breast cancer (BC) is a major global health concern, with genetic factors contributing significantly to individual risk. The MTHFR C677T (rs1801133) polymorphism has been extensively studied for its potential role in BC susceptibility; however, results have been inconsistent, particularly in the United States (US). Therefore, this study evaluates the association between the C677T variant and BC risk exclusively in populations from the US by pooling data from published case–control studies. A systematic literature search was conducted across multiple online resources to identify relevant studies published up to 2025. Eleven case–control studies comprising 9,137 BC cases and 12,427 controls were included. Genotypic and allelic data were extracted, and pooled odds ratios with 95% confidence intervals were calculated under different genetic models. Study quality was assessed using the Newcastle–Ottawa Scale, and heterogeneity and publication bias were examined. The pooled analysis showed no significant association between the C677T polymorphism and BC risk across different genetic models (allele model: odds ratio = 1.02, 95% confidence interval = 0.96–1.08, p = 0.493, adjusted p-value = 1) in the US population. Sensitivity analyses further confirmed the stability and robustness of these findings. Furthermore, heterogeneity across studies was low to moderate, and no evidence of significant publication bias was detected. In conclusion, this updated meta-analysis suggests that the MTHFR C677T variant is not significantly associated with BC susceptibility in US populations. Further research with larger sample sizes and considering gene–environment interactions is warranted to clarify the complex genetics of breast cancer risk.