mid-14c., knokel "finger joint; any joint of the body, especially a knobby one; morbid lump or swelling." Perhaps in Old English, but not attested there. Common Germanic (compare Middle Low German knökel, Middle Dutch cnockel, German knöchel), literally "little bone," a diminutive of Proto-Germanic root *knuk- "bone," which is not represented in English in its simple form (but compare German Knochen "bone). For pronunciation, see kn-.
1740, from knuckle (n.), originally in the game of marbles (putting a knuckle on the ground is the hand position preliminary to shooting). To knuckle down "apply oneself earnestly" is 1864 in American English, an extended sense from marbles; to knuckle under "submit, give in" is first recorded 1740, supposedly from the former more general sense of "knuckle" and here meaning "knee," hence "to kneel."