The aim of this study was to determine a cost-effective diagnostic method for lumbar herniated disc with knee osteoarthritis (LHD-KOA) based on aberrant outcome measures, levels of biomarkers, and examination of the lower-extremity. Data were separately analyzed for each cohort suffering with LHD-KOA (n = 108; 59.82 ± 7.15 years) and without LHD-KOA (n = 108; 58.81 ± 7.61 years), and findings were confirmed with radiological images. The aberrant-leg-features (bilateral: knee gaps between the short head of biceps femoris and the surface of the bed, diameters of calves and thighs, angles of straight leg raising, knee-flexion and -extension in a supine position) and biochemical parameters (Interleukin-10, Tumor necrosis factor-alpha, C-reactive protein, creatine kinase-muscle, and Aldolase-A), and outcome measures, Western Ontario and McMaster Universities osteoarthritis index (WOMAC), knee-injury osteoarthritis outcomes scale (KOOS), Oswestry disability index (ODI), and body mass index (BMI)for participants with and without LHD-KOA were evaluated with appropriate techniques. All the subjects underwent standardized physical examination and completed a questionnaire. The risk ratios and mean ± standard deviations of biomarkers, anatomical features, and outcome measures of the experimental subjects were highly significant compared to controls (p < 0.0001). Results suggest that monitoring the studied aberrant outcome measures, biomarkers, and lower-anatomical features may be a cost-effective diagnostic tool for LHD-KOA. Further research is recommended for an alternative treatment protocol for LHD-KOA.