The 23-year-old Englishman shot a closing six-under 64 to end on 14-under at Crans-sur-Sierre Golf Club in Switzerland.
Hend led by three shots going into round four and had an eight-foot putt to win on the second playoff hole, but he missed.
He then hit the grandstand from the bunker at the third playoff hole and saw his next chip finish inches from the water on his way to a bogey-five.
This allowed Fitzpatrick to snatch victory with a two-putt par and condemn Hend to defeat at the event's playoff stage for a second consecutive year.
Tyrrell Hatton birdied four of his final seven holes to join Fabrizio Zanotti in a share of third spot on 11-under, with Mikko Ilonen a further stroke back in fifth spot after a joint-low round-of-the-day 64.