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Introduction: Chronic pain (CP) is a complex multidimensional experience severely affecting individuals' quality of life. Multiple cognitive, affective, emotional, and interpersonal factors play a major role in CP. Furthermore, the psychological, social, and physical circumstances leading to CP show high inter-individual variability, thus making it difficult to identify core syndrome characteristics. In a biopsychosocial perspective, we aim at identifying a pattern of psycho-physical impairments that can reliably discriminate between CP individuals and healthy controls (HC) with high accuracy and estimated generalizability using machine learning., Methods: A total of 118 CP and 86 HC were recruited. All individuals were administered several scales assessing quality of life, physical and mental health, personal functioning, anxiety, depression, beliefs about medical treatments, and cognitive ability. These features were trained to separate CP from HC using support vector classification and repeated nested cross-validation., Results: Our psycho-physical classifier was able to discriminate CP from HC with 86.5% balanced accuracy and significance (p = 0.0001). The most reliable features characterizing CP were anxiety and depression scores, and belief of harm from prolonged pharmacological treatments; for HP, the most reliable features were physical and occupational functioning, and vitality levels., Conclusion: Our findings suggest that, using psychological and physical assessments, it is possible to classify CP from HC with high reliability and estimated generalizability via (i) a pattern of psychological symptoms and cognitive beliefs characteristic of CP, and (ii) a pattern of intact physical functioning characteristic of HC. We think that our algorithm enables novel insights into potential individualized targets for CP-related early intervention programs.