This study investigates the clinical value of plasma Septin-9 gene methylation (mSEPT9) and carcinoembryonic antigen (CEA) in colorectal cancer (CRC), and their correlations with clinicopathological features and recurrence. A retrospective study included 81 CRC patients (observation group) and 73 healthy controls (comparison group) from January 2021 to January 2023, with pathological diagnosis as the gold standard. Plasma mSEPT9 (via quantitative PCR) and CEA (via electrochemiluminescence) levels were measured. Associations between mSEPT9 Ct values/CEA status and clinicopathological parameters (tumor location, metastasis, tumor diameter, etc) were analyzed. The observation group was followed for 1 year to assess the relationship between persistent positivity of mSEPT9/CEA before and after surgery and recurrence/metastasis. CEA positivity was significantly associated with tumor location (P < .0001), distant metastasis (P < .0001), and lymph node metastasis (P < .0001). mSEPT9 positivity correlated with distant metastasis (P = .009) and tumor diameter >= 5 cm (P = .001). Compared with negative cases, mSEPT9-positive individuals had a 12.08-fold higher risk of CRC (OR = 12.079; 95% CI = 3.699-39.447, P < .001), and CEA-positive individuals had a 5.30-fold higher risk (OR = 5.301; 95% CI = 1.339-20.981, P = .017). Postoperative persistent mSEPT9 positivity showed a stronger association with recurrence/metastasis than CEA (chi(2) = 7.227, P = .007 vs chi(2) = 5.739, P = .017). Combined detection of mSEPT9 and CEA achieved an area under the curve of 0.829, with sensitivity of 78.00% and specificity of 90.00%, outperforming single-marker analysis. Both mSEPT9 and CEA positivity are independent risk factors for CRC. mSEPT9 is closely linked to tumor burden and distant metastasis, demonstrating higher sensitivity in monitoring postoperative recurrence.