indefatigable (adj.)

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" (see de-) + fatigare "to weary" (see fatigue (n.)).

Blount's "Glossographia" (1656) has defatigable, which also was in use elsewhere in 17c., but the modern use of defatigable (1948) probably is a jocular back-formation from indefatigable.