'musculoskeletal' is formed from the combining form 'musculo-' from Latin 'musculus' (meaning 'little mouse', used for 'muscle') and English 'skeletal' from Greek/Latin 'skeleton'/'skeletos'.

'musculus' (Latin, 'little mouse') gave rise to the Neo-Latin/Latin 'muscle' and 'musculo-' combining form; 'skeletos' (Greek, 'dried') passed into Latin as 'skeleton' and into English via Old French and Late Latin, and the two elements were combined in modern English to form 'musculoskeletal'.

Initially the roots referred to 'muscle' (via Latin 'little mouse') and 'skeleton' (dried body); over time the combined form came to mean 'pertaining jointly to muscles and the skeleton' in anatomy and medicine.