mid-15c., muscheron, musseroun (attested 1327 as a surname, John Mussheron), from Anglo-French musherun, Old French meisseron (11c., Modern French mousseron), perhaps from Late Latin mussirionem (nominative mussirio), though this might as well be borrowed from French. Barnhart says "of uncertain origin." Klein calls it "a word of pre-Latin origin, used in the North of France;" OED says it usually is held to be a derivative of French mousse "moss" (from Germanic), and Weekley agrees, saying it is properly "applied to variety which grows in moss," but Klein says they have "nothing in common." For the final -m Weekley refers to grogram, vellum, venom. Modern spelling is from 1560s.
Used figuratively for something or someone that makes a sudden appearance in full form from 1590s. In reference to the shape of clouds after explosions, etc., it is attested from 1916, though the actual phrase mushroom cloud does not appear until 1955.