'anti-confederation' originates from combining the prefix 'anti-' (from Greek 'anti' meaning 'against') with 'confederation' (ultimately from Latin 'confoederatio'), the latter via Old French and Middle English.

'confederation' changed from Old French 'confederacion' into Middle English 'confederacioun' and eventually became the modern English 'confederation'; the prefix 'anti-' (Greek 'anti') was attached in modern usage to form compounds such as 'anti-confederation'.

Initially it meant 'being against the formation of a confederation (a league or union of states or groups)', and over time it has retained that core meaning as an adjective or noun describing opposition to confederation.