1530s, transitive, "unite or blend promiscuously into one mass, body, or assemblage," a back-formation from Middle English myxte (early 15c.) "mingled, blended, composed of more than one element, of mixed nature," from Anglo-French mixte (late 13c.), from Latin mixtus, past participle of miscere "to mix, mingle, blend; fraternize with; throw into confusion," from PIE root *meik- "to mix."
A rare verb before Elizabethan times. Perhaps it was avoided out of potential confusion with a group of common Middle English words such as mixen "dung-hill, pile of refuse," mix "filth, dung, dirt" mixed "foul, filthy," from PIE root *meigh- "to urinate" (source of Latin mingere, etc.).
Meaning "to form by mingling or blending different ingredients" is from 1570s. Intransitive sense of "become united or blended promiscuously" is from 1630s; that of "become joined or associated" is from 1660s. In cinematography and broadcasting, "combine two pictures or sounds by fading out and in," 1922. Old English as miscian (apparently borrowed from the Latin verb) did not survive into Middle English. Related: Mixed; mixing.