Background & Aims: Accurate and noninvasive diagnosis and staging of liver fibrosis is essential for effective clinical management of chronic liver disease (CLD). We aimed to identify serum metabolite markers that reliably predict the stage of fibrosis in CLD patients. Methods: We quantitatively profiled serum metabolites of participants in 2 independent cohorts. Based on the metabolomics data from Cohort 1 (504 HBV associated liver fibrosis patients and 502 normal controls, NC), we selected a panel of 4 predictive metabolite markers. Consequently, we constructed 3 machine learning models with the 4 metabolite markers using random forest (RF), to differentiate CLD patients from normal controls (NC), to differentiate cirrhosis patients from fibrosis patients, and to differentiate advanced fibrosis from early fibrosis, respectively. Results: The panel of 4 metabolite markers consisted of taurocholate, tyrosine, valine, and linoelaidic acid. The RF models of the metabolite panel demonstrated the strongest stratification ability in Cohort 1 to diagnose CLD patients from NC (area under the receiver operating characteristic curve (AUROC) = 0.997 and the precision-recall curve (AUPR) = 0.994), to differentiate fibrosis from cirrhosis (0.941, 0.870), and to stage liver fibrosis (0.918, 0.892). The diagnostic accuracy of the models was further validated in an independent Cohort 2 consisting of 300 CLD patients with chronic HBV infection and 90 NC. The AUCs of the models were consistently higher than APRI, FIB-4 and AST/ALT ratio, with both greater sensitivity and specificity. Conclusion: Our study showed that this 4-metabolite panel has potential usefulness in clinical assessments of CLD progression.