'anti-vaccinationist' originates from English, specifically the combination of the prefix 'anti-' (from Greek 'anti' meaning 'against'), the noun 'vaccination' (from Latin 'vaccinus', related to 'vacca' meaning 'cow' via the term coined for cowpox-based inoculation), and the agentive suffix '-ist' (from Greek/Latin, denoting a person who practices or advocates).

'anti-vaccinationist' developed in the 19th century as organized opposition emerged after the introduction of smallpox vaccination; the element 'vaccination' itself was coined in the late 18th/early 19th century from Latin 'vaccinus' (of the cow) and the modern English formation combined it with 'anti-' and '-ist' to denote a person opposed to vaccination.

Initially associated specifically with opposition to early smallpox vaccination, the term's meaning broadened over time to refer to opposition to vaccination in general, including modern immunizations and vaccine policies.