1580s (implied in indefatigably), from French indefatigable (15c.), from Latin indefatigabilis "that cannot be wearied," from in- "not" (see in-(1)) + defatigare "to tire out," from de- "utterly, down, away" + fatigare "to weary" (see fatigue). Blount (1656) has defatigable, which was in use in 17c. Modern use (1948) probably is a jocular back-formation from indefatigable.