1550s in a literal sense "mix or mingle things or ideas so as to render the elements indistinguishable;" from mid-18c. in the active, figurative sense of "perplex the mind or ideas of, discomfit in mind or feeling," but not in general use until after c. 1800. From 1862 as "erroneously regard as identical." It took over these senses from its older doublet, confound (q.v.).
The past participle confused (q.v.) is attested much earlier, in Middle English (serving as an alternative past tense to confound), evidently an adaptation of Old French confus or Latin confusus, "with the native ppl. ending -ED and the present stem a much later inference from it" [OED]. Related: Confusing.