The 21-year-old Englishman was locked in an enthralling race for the title with Dane Soren Kjeldsen until pressing the turbo-charge button on the back nine and accelerating away from the field to finish with a 68 and a 15-under total of 269.
Fitzpatrick, who had held or shared the lead all week, snared successive birdies at the 11th and 12th before rolling home a 20-foot birdie effort at the 15th and turning to the crowd to celebrate with a double fist-pump.
The former world amateur number one effectively sealed his maiden tour win with a laser-guided tee shot to three feet at the short 17th and could even afford the luxury of a dropped shot at the last on a sunny but cold autumnal day at Woburn.
Kjeldsen looked as if he would make Fitzpatrick fight all the way to the 18th but his bid was undermined when he took three putts from 30 feet at the 15th and followed up by slicing his drive straight up against a tree at the next hole.
The Dane ended up with a 69 for 271 and had to settle for a share of second place with Ireland's Shane Lowry (67) and Paraguay's Fabrizio Zanotti (69).
GREAT DAY
"It's not going to sink in for a long time," Fitzpatrick told the presentation ceremony after picking up a cheque for $755,000 and doubling his earnings for the season.
"It was a long day and I didn't really know what I had to do to win but I just sort of ground it out. It was a great day."
More than 57,000 fans attended the four days as the tournament returned to the circuit following a seven-year absence.
"The fans have just been incredible to me and unbelievably supportive and I can't tell everyone how appreciative I am of that," said Fitzpatrick after becoming the youngest winner of an event that has been on the tour since 1972.
"Walking down every hole it's, 'Come on Matt' and it's amazing to have that support," added the Englishman who will now climb from 111th in the world rankings into the top 60.
Kjeldsen, who won the Irish Open in May, said he found it difficult to read the putting surfaces.
"I played great today but I struggled on the greens," said the 40-year-old. "I'm extremely pleased how I played but disappointed how I putted.
"It's been an absolutely brilliant week, a great venue, great atmosphere, fantastic facilities. It's just a joy to come here and I can't wait to come back."
(Editing by Ed Osmond/Mitch Phillips)
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