'anti-confederationist' originates from English, formed by the prefix 'anti-' (from Greek 'anti' meaning 'against'), the noun 'confederation' (from Latin roots 'con-' meaning 'together' and 'foedus/foederatio' meaning 'treaty' or 'league'), and the agentive suffix '-ist' (from Greek/Latin use meaning 'person who').

'anti-confederationist' arose in political English in the 19th century (notably during debates about Canadian and other colonial confederations) as a compound describing opponents of proposals to unite separate political units; it follows the pattern of compounds like 'anti-federalist' and other political labels formed by prefix + noun + suffix.

Initially and historically it meant 'a person opposed to a particular plan of confederation'; that specific political sense remains its principal meaning in modern usage.