The word 'tsetse' entered English in the mid-19th century, borrowed directly from the Tswana language of southern Africa. It is a classic example of a loanword adopted to name a geographically specific organism for which no prior English term existed. The term's journey reflects European colonial and scientific exploration of Africa, where the fly's significant impact on human and animal health necessitated its precise identification. The spelling was anglicized from the original Tswana tsêtsê, but the word remains unanalyzable into meaningful English or classical morphemes, retaining its status as a borrowed simplex noun.

This word is a simplex loanword. It originates from the Tswana language (a Bantu language of southern Africa), from the word tsêtsê, meaning "fly."