late 14c., of persons; 1650s of tools, etc., from left (adj.) + -handed. In 15c. it also could mean "maimed." Sense of "underhanded" is from early 17c., as in left-handed compliment (1787, also attested 1855 in pugilism slang for "a punch with the left fist"), as is that of "illicit" (as in left-handed marriage). Related: Left-handedly; left-handedness.
