Background: Matrix metalloproteinases (MMPs) have emerged as potential biomarkers in osteoarthritis (OA) progression, yet their clinical utility remains under investigation. This study evaluated the diagnostic and prognostic potential of MMP-1, MMP-3, and MMP-13 in OA progression and their correlation with clinical parameters. Methods: A prospective observational study was conducted over six months, involving 270 patients (ages 40-70 years) with primary knee OA. Serum MMP levels were quantified using ELISA, while disease severity was assessed using WOMAC index, VAS pain scores, and Kellgren-Lawrence (K-L) grading. Statistical analysis included correlation coefficients and multiple regression analysis. Results: Significant elevations in MMP levels were observed with increasing K-L grades, particularly for MMP-13 in advanced OA (9.8 ± 2.3 ng/mL in K-L grades 3-4 vs 4.6 ± 1.2 ng/mL in grades 1-2, p<0.001). Strong correlations were found between MMP-13 levels and WOMAC scores (r=0.76, p<0.001). Multiple regression analysis identified K-L grade as the strongest predictor of elevated MMP levels (β=0.56, p<0.001), followed by BMI (β=0.42, p<0.001). Pain severity showed significant association with MMP-13 levels, particularly in severe cases (12.6 ± 2.8 ng/mL). Conclusion: The study demonstrates strong correlations between MMP levels, particularly MMP-13, and OA severity markers, supporting their potential as diagnostic and prognostic biomarkers. These findings suggest the utility of MMP profiling in early disease detection and monitoring, potentially enabling more targeted therapeutic approaches in OA management.