'musculo-skeletal' is formed from the combining form 'musculo-' (from Latin 'musculus' meaning 'little mouse', used for 'muscle') and 'skeletal' (from Greek 'skeletos' meaning 'dried' via Latin and Old French), reflecting the components 'muscle' + 'skeleton'.

'musculo-' developed as a New Latin combining form from Latin 'musculus'; 'skeleton' comes from Greek 'skeletos' via Latin and Middle English; the compound 'musculoskeletal' (modern English) arose by combining these elements in medical/technical usage.

Initially the parts referred separately to 'muscle' and 'skeleton'; over time the compound came to mean jointly 'relating to both muscles and the skeleton', especially in clinical contexts (e.g., musculoskeletal system, musculoskeletal disorder).