AFP Sport looks back at his previous six championship matches at the tournament, a run which has yielded two wins and four defeats.
- 2012: lost to Rafael Nadal (ESP) 6-4, 6-3, 2-6, 7-5 -
In a final pushed into a third week for only the second time because of rain on the Sunday, Nadal, playing in his 16th Grand Slam final, took his Paris record to a staggering 52 wins against just one loss.
Victory, which was achieved on a Djokovic double fault, allowed him to break the tie for six French Opens he shared with Bjorn Borg.
For five-time major winner Djokovic, the Wimbledon, US Open and Australian Open champion, it was the end of his dream of emulating Don Budge (1938) and Rod Laver (1962 and 1969) by holding all the Grand Slams at once.
He was left to regret his unforced error count of 53 which undermined his challenge.
- 2014: lost to Rafael Nadal (ESP) 3-6, 7-5, 6-2, 6-4 -
Nadal clinched his ninth French Open and 14th career Grand Slam title, becoming the first man to win five Roland Garros crowns in succession.
"Every moment was crucial, all the points were so hard," said Nadal.
Djokovic dominated the early stages of the final, the pair's 42nd meeting, seemingly immune to the sweltering 30-degree heat on Philippe Chatrier court.
But Nadal, playing in his 20th Grand Slam final to Djokovic's 13th, grew stronger as the final wore on as he ended a four-match losing streak against his old rival.
The 3hr 31min duel ended on a sour note when Djokovic double-faulted on match point, shaken by a shout from the crowd.
- 2015: lost to Stan Wawrinka (SUI) 4-6, 6-4, 6-3, 6-4 -
Djokovic saw his dreams of becoming just the eighth man to claim a career Grand Slam shattered again despite being the overwhelming favourite to beat Wawrinka, just as he had done in 17 of 20 previous clashes.
"I'm proud of the fight that I put into this match. It wasn't to be," said Djokovic whose Grand Slam tally at that stage remained at five Australian Opens, two Wimbledon titles and a single triumph at the US Open.
Djokovic was in tears on the presentation podium as the 15,000-capacity crowd inside Court Philippe Chatrier afforded him a lengthy standing ovation.
"It gives me even more motivation to come back and keep on trying."
- 2016: defeated Andy Murray (GBR) 3-6, 6-1, 6-2, 6-4 -
Djokovic captured a first French Open and a 12th career major, joining Don Budge in 1938 and Rod Laver, in 1962 and 1969, as the only players to simultaneously possess the French Open, Australian Open, US Open and Wimbledon trophies.
But he did it the hard way as the final reached a tense conclusion, being broken in the eighth game of the fourth set as he served for the title and then squandering two championship points in the 10th before sealing victory when Murray netted a backhand.
"When I broke him the second time and I got to 5-2 in the fourth, I just started laughing. I had that kind of emotion. I didn't feel too much pressure, honestly," said Djokovic, one of only eight men to complete the career Grand Slam.
- 2020: lost to Rafael Nadal (ESP) 6-0, 6-2, 7-5 -
Nadal demolished Djokovic to win his 13th French Open and go level with Roger Federer on 20 majors. He also claimed his 100th match win at Roland Garros against just two defeats since his 2005 debut.
The Spaniard, the oldest champion in Paris since Andres Gimeno in 1972, claimed the title without dropping a set.
He finished the one-sided affair with just 14 unforced errors to his opponent's 52.
The 56th meeting between the two players started under the roof of Court Philippe Chatrier, intensifying the echo of a crowd limited to 1,000 due to the pandemic. The tournament had been postponed earlier in the year because of the global health crisis.
- 2021: defeated Stefanos Tsitsipas (GRE) 6-7 (6/8), 2-6, 6-3, 6-2, 6-4 -
Djokovic claimed a 19th Grand Slam title and became the first man in 52 years to win all four majors twice after a four-hour and 11-minute triumph.
He also became the first man since Rod Laver in 1969 to win all four Slams on multiple occasions and just the third in history.
"It was an electric atmosphere. I want to thank everyone who has been with me on this journey," said Djokovic who was also the first man ever to win a Slam title by twice coming back from two sets down following his last-16 victory over Italy's Lorenzo Musetti.
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