Mechanism-based classification of pain has been advocated widely to aid tailoring of interventions for individuals experiencing persistent musculoskeletal pain. Three pain mechanism categories (PMCs) are defined by the International Association for the Study of Pain: nociceptive, neuropathic, and nociplastic pain. Discrimination between them remains challenging. This study aimed to build on a framework developed to converge the diverse literature of PMCs to systematically review methods purported to discriminate between them; synthesise and thematically analyse these methods to identify the convergence and divergence of opinion; and report validation, psychometric properties, and strengths/weaknesses of these methods. The search strategy identified articles discussing methods to discriminate between mechanism-based categories of pain experienced in the musculoskeletal system. Studies that assessed the validity of methods to discriminate between categories were assessed for quality. Extraction and thematic analysis were undertaken on 184 articles. Data synthesis identified 200 methods in 5 themes: clinical examination, quantitative sensory testing, imaging, diagnostic and laboratory testing, and pain-type questionnaires. Few methods have been validated for discrimination between PMCs. There was general convergence but some disagreement regarding findings that discriminate between PMCs. A combination of features and methods, rather than a single method, was generally recommended to discriminate between PMCs. Two major limitations were identified: an overlap of findings of methods between categories due to mixed presentations and many methods considered discrimination between 2 PMCs but not others. The results of this review provide a foundation to refine methods to differentiate mechanisms for musculoskeletal pain.