'O-deethylation' is built from chemical-nomenclature elements: the prefix 'O-' (the letter O indicating oxygen), 'de-' from Latin meaning 'removal', 'ethyl' (from modern chemical term 'éthyl' ultimately from Greek roots related to 'ether'), and the noun-forming suffix '-ation' (from Latin '-ationem') indicating an action or process.

'O-deethylation' arose in 20th-century biochemical and pharmacological usage by adding the specifying prefix 'O-' to the established chemical term 'deethylation' (itself from 'de-' + 'ethyl' + '-ation'). As metabolic studies developed, the term became standard to describe enzymatic removal of O-linked ethyl groups.

Originally, 19th-century chemical terminology 'deethylation' described the removal of an ethyl radical in organic reactions; over time it evolved into the biochemical sense of enzymatic metabolic removal of an O-bound ethyl group (i.e., a metabolic dealkylation of oxygen-bound ethyl substituents).