Objective To evaluate the clinical application value of combined detection of anti-cyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) in the early diagnosis of rheumatoid arthritis (RA). Methods A total of 30 RA patients (RA group), 30 non-RA patients (non-RA group), and 20 healthy controls (healthy group) were enrolled. Serum levels of anti-CCP antibody, RF, and anti-keratin antibody (AKA) were measured, and their positive rates were compared among groups. Using the RA group as the diagnostic reference, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), and area under the ROC curve (AUC) were analyzed for individual and combined markers. Results The positive rates of anti-CCP, RF, and AKA in the RA group were 76.7%, 83.3%, and 63.3%, respectively, significantly higher than those in the other two groups (P < 0.05). Combined detection of anti-CCP and RF showed a sensitivity of 90.0%, specificity of 80.0%, and an AUC of 0.850, outperforming single-marker detection (P<0.05). Conclusion The combined detection of anti-CCP antibody and RF demonstrates good sensitivity and high consistency in the early diagnosis of RA, effectively improving identification efficiency. It is recommended that this combined application be promoted in clinical practice.