'aortosclerosis' originates from Greek, specifically the combining form 'aorto-' from Greek 'aortē' meaning 'artery' and 'sclerosis' from Greek 'sklērōsis', where 'sklēr-' meant 'hard'.

'aortosclerosis' was formed in modern medical English by combining the New Latin/Greek-derived elements 'aorto-' and 'sclerosis'; both elements entered medical usage via Latin and New Latin in the 18th–19th centuries and were combined in 19th–20th century clinical literature to denote hardening of the aorta.

Initially, the Greek root for 'skler-' referred broadly to 'hardness'; in modern medical usage the compound specifically denotes 'hardening of the aorta'.