Knuckle comes from ME knokel, akin to D kneukel, G Knochel, dim. of a word represented by D knok, G Knochen, meaning "bone," so I surmise that knucklehead is just another way of saying, as Dr Bill's post hints, bonehead.

BTW - knuckle down comes from the game of marbles, referring to the concentration of purpose manifested in a player who is on the floor, knuckle against the ground, preparing a shot, and knuckle under comes from the idea of bowing, knee to floor, in submission.