The Englishman had entered the final round with a two-shot advantage but Dane Bjerregaard carded a stunning seven-under-par 63 to set a target at 17-under overall.
Another birdie at the same hole ensured he became the first player since Spanish great Seve Ballesteros in 1978 to win back-to-back titles at Crans-sur-Sierre Golf Club in Switzerland.
"This is what I wanted to achieve this season -- another win," Fitzpatrick said. "To get it here again is so special and to get my fifth is amazing. I love this place.
"Of all my wins I'd say that was definitely the most difficult. I didn't have my A game today; despite loving this place I just didn't play my best today. I managed to grind it out, made some crucial birdies coming in and I'm delighted."
At 24 years and eight days old, Fitzpatrick becomes the youngest Englishman to claim five European Tour victories, having lifted a title in every season since coming through qualifying school in 2014.
Frenchman Mike Lorenzo-Vera finished third with 15 under for the tournament, three shots clear of Spaniard Nacho Elvira and four ahead of England's Daniel Brooks.
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