The 21-year-old entered the final day four shots off the lead and did not look a likely winner as he turned in level par at Le Golf National.
But three birdies in four holes to start the back nine put him in a share of the lead and he added two more at the difficult 15th and 17th to sign for a 66 and finish at 14 under, two shots clear of England's Jordan Smith and Dane Jeff Winther.
Dane Rasmus Højgaard was then at 11 under, one clear of Austria's Lukas Nemecz and two ahead of home favourite Julien Brun, Japan's Kazuki Higa, South Korean Tom Kim and German Yannik Paul.
Isao Aoki was Japan's first DP World Tour winner at the 1983 Panasonic European Open and it would be 33 years before there was another thanks to Hideki Matsuyama's victory at the WGC-HSBC Champions.
Matsuyama would add another World Golf Championships title the following year at the WGC-Bridgestone Invitational before sealing his country's greatest golfing moment by triumphing at the Masters Tournament in 2021.
Hisatsune can now add his name to that roll of honour, as he enjoys a brilliant rookie season after securing his card less than 12 months ago at the Qualifying School.
He finished second at the Fortinet Australian PGA Championship and added five more top tens before claiming this first win which moves him to 11th in the Race to Dubai Rankings in Partnership with Rolex and could put him inside the top 100 on the Official World Golf Ranking for the first time.
"It feels unreal," he said. "For me, I didn’t think I would win, but I just won! I’m feeling delighted, it’s my first win, I’m so happy. I fly back to Japan tomorrow. Maybe in business class, I don’t know!
"The front nine I did not play well, but the back nine I played very well. I think this was because I wanted to win.
"It’s been nothing like I thought (DP World Tour career so far). I only turned pro three years ago, first years playing in Japan, then on to the DP World Tour through Q School. Now I’m here with my first win in my pro career – it’s so amazing."
Overnight leader Smith put his approach on the first to ten feet before holing an 18-footer on the second to get to 15 under and, with co-leader Ewen Ferguson finding water at both holes to record a pair of double-bogeys, the 30-year-old led by six.
But he three-putted the fourth and failed to get up and down on the eighth and 11th after missing the green to slip back to 12 under where he was soon in a four-way tie.
Hisatsune had turned in level par as he bounced back from bogeys at the fourth and eighth with a 26-footer on the fifth and a two-putt gain on the ninth.
He then came to life after the turn, holing from 25 feet at the tenth and putting irons inside three feet on the 12th and 13th to join the lead.
Winther holed a long putt on the first but gave the shot back on the fourth before he put approaches inside ten feet on the fifth and sixth.
He then holed from the rough for eagle at the ninth, made a long putt on the tenth and got up and down on the 14th to share the lead.
A bogey at the 17th was followed by an incredible approach to three feet on the last and Winther was left to wait and see after signing for a 65.
What he saw was Hisatsune stick a stunning approach to ten feet at the 15th and then follow it up with an equally good one on the 17th to take the title as Smith parred his way home in a 72.
Højgaard had shared the lead when he made his sixth birdie of the day on the 13th but he dropped a shot on the 16th to go with two bogeys on the front nine in a 68, a score matched by Nemecz who made four birdies around the turn after bogeying the first.
Kim signed for a 68 and Brun carded a 70 while Paul and Higa endured disappointing afternoons with rounds of 73 and 74 respectively.
Scot Ferguson added two bogeys and a birdie to his poor start in a 76 that left him at eight under alongside countryman Calum Hill, South African Zander Lombard and Dane Thorbjørn Olesen.