Fleetwood birdied the first hole of a sudden-death play-off on the Centenary Course at Gleneagles to edge out Scotland's Stephen Gallacher and Argentina's Ricardo Gonzalez after a dramatic final round.
Gallacher looked out of contention when he ran up a triple-bogey seven on the 11th, but bounced back with birdies at the 14th and 16th and then holed from 15ft for an eagle on the last.
That set the clubhouse target at 18 under par and Fleetwood matched it thanks to an eagle of his own on the 16th and birdie on the last, with playing partner Gonzalez making birdies on the 16th and 18th after almost holing his bunker shot on the last for a winning eagle.
The players returned to the par-five 18th for the play-off and Gallacher was eliminated when he failed to get up and down from a greenside bunker, missing a birdie putt from seven feet.
Gonzalez, who needed treatment on a knee injury during the round, had putted down to five feet from just off the back of the green and when he also missed, Fleetwood was left to hole from four feet for a winning birdie and the first prize of £233,330.
"The other two guys were a little unlucky with their putts and before you know it you have a four footer for the win," said Fleetwood, who carded a closing 70.
"God knows how I made contact. It all seemed to unravel really quickly."
Ryder Cup qualifying starts at the Wales Open this week and Fleetwood added: "I wish the points started a week earlier, but there are a lot of players that are a long way ahead of me in the running for a Ryder Cup spot.
"All I can do is keep trying to improve every week and keep playing as good as I can, but the Ryder Cup is a long way off. It's obviously a lifetime goal and something I would love to do, but whether that's next year or in three or five years' time it doesn't really matter as long as I can play and achieve a goal.
"But next year would be lovely for sure."
Fleetwood was the youngest winner of the Challenge Tour in 2011 but only kept his card at the end of his rookie season on the European Tour thanks to a first top-10 finish of the year in the final event in South Africa.
The 22-year-old from Southport, who stayed with his parents in a house behind the 12th green this week, added: "I have been up there a lot and not even had a top-five finish and all of a sudden you come away with a win. It's absolutely amazing."
Gallacher, whose participation had been in doubt all week due to a back injury suffered washing his car on Monday, said: "I would have taken a play-off on Monday.
"On the 18th I knew I needed to hole it (his eagle putt) to have a chance. It was a great putt, just a shame I could not do it again."