Djokovic's defeat means the 39-year-old Serb's wait to go past Margaret Court's mark will continue in the twilight of his glorious career, and also further opens up the draw in Paris a day after world number one Jannik Sinner's shock exit.
Victory in an epic clash lasting seven minutes short of five hours ensured Fonseca became the first teenager to beat Djokovic in a Grand Slam match as he announced himself as another genuine contender to claim a maiden major crown.
"I actually didn't believe I could win the match, I just played and enjoyed being on the court. What an idol we have, and what a pleasure it was to step on the court against him, so I thank him. I'm very happy," Fonseca said.
"I was just trying to hit the ball as fast as I could, I mean Djokovic doesn't miss and we still think he's 20. At the end of the match, he was more fit than me, which is crazy, and when the day was getting darker, I felt much slower."
Fonseca dedicated the hard-fought victory to his mother, who was beaming in the stands on her birthday.
Roland Garros was also assured a first-time major winner, with defending champion Carlos Alcaraz skipping the tournament due to a wrist injury.
A week after turning 39, Djokovic began strongly and played like a younger version of himself as he comfortably won five of the opening six games and put down a marker in the first set on a sun-drenched Court Philippe Chatrier.
The Serb produced a stunning lob, a couple of heavy forehand winners and two delightful drops in that spell, almost schooling his 19-year-old opponent on the art of playing on Parisian clay, and wrapped up the set after a late Fonseca comeback attempt.
Fonseca, who was still in his crib when Djokovic lifted his first Grand Slam title at the 2008 Australian Open, went toe-to-toe with his senior colleague in the next set only to drop his serve in the fifth game.
It was the opening Djokovic needed, and the third seed took full control, letting out a roar when he went up 5-3 and pumping his fists after he closed out the set with a sharp passing shot through the middle.
Fonseca raised his level to pull a set back and then broke early in the fourth, drawing thunderous applause from his fans, before levelling up the match at two sets all with some fiery ball-striking that at times left Djokovic in disbelief.
The Brazilian came from 1-3 down in the decider and showed nerves of steel to stay level after 10 games and then break for a 6-5 lead, which gave him the perfect platform to close out a famous victory with three straight aces.
"I just believed that I could do the aces, it was crazy," Fonseca said. "I have never done that before. I'm super happy that I could finish like this.
"I felt like John Isner."
