The Serbian's 1-6, 6-3, 6-1 defeat also ended his dream of winning an Olympic singles gold medal, the only major honour missing from his long list of accolades.
Federer decided to end his Roland Garros campaign on Sunday, a day after winning a gruelling third-round match against Dominik Koepfer.
Images from Day 11 of the 2021 French Open at Roland Garros in Paris on Wednesday.
'When she hits her peak she's so dangerous because she moves well.'
Looking to improve her claycourt skills, she spent a bit of time at 11-time French Open champion Rafael Nadal's academy.
Djokovic did not play badly in the final but it took him 55 minutes before he registered his first game in what turned out to be a mauling.
Images from Day 5 of the 2021 French Open, in Paris, on Thursday.
'I have a lot of other goals, dreams that are in my mind and within my team and we'll certainly reset in the next couple of days ... enjoy some time together and then we go again. But really looking forward to the Olympics.'
Factbox on Rafael Nadal, who beat Dominic Thiem 6-4, 6-3, 6-2 to win his 11th French Open title on Sunday:
Djokovic has won the last three editions of Wimbledon in 2018, 2019 and last year
Five things to watch out for on day five of the French Open on Thursday
It's on! Rafael Nadal and Novak Djokovic are set to clash in the French Open quarterfinal on Wednesday.
Rafael Nadal said on Friday that he intends to compete at Wimbledon later this month
Rafael Nadal returns to the US Open for the first time in three years short of match practice and with big question marks about his fitness but few people will dismiss the Spaniard's chances of claiming a record-extending 23rd Grand Slam title.
Tsitsipas pulled out of the Wimbledon warm-up event in Halle, Germany, because of personal reasons
Krejcikova became the first player to win both the women's singles and doubles title in Paris since Mary Pierce completed the feat in 2000.
'Serena must be prepared to live with it and say goodbye even in the face of defeat'
Indian Wells organisers said on Tuesday that world number two Novak Djokovic had been placed in the tournament's draw but it was unclear if the Serbian would be permitted to enter the United States.
Monfils said all players were not similarly equipped to deal with the pressure of being a top athlete.
The motto 'if at first you don't succeed' might have been coined for Japan's Yuichi Sugita, who after a battling French Open main draw debut on Sunday finds himself close to reaching the second round of a Grand Slam for the first time.
* Swiatek started playing tennis in an attempt to emulate her older sister, who competed briefly on the junior circuit.
World number one Novak Djokovic said his win over Rafa Nadal in Friday's epic French Open semi-final was one of the top three matches he had played and he would remember it forever.
Swiatek made the most of Kasatkina's string of unforced errors, peppering court Philippe Chatrier with winners.
World number one Andy Murray will be ready for Roland Garros despite his poor recent form, nine-time French Open champion Rafael Nadal has said.
Shapovalov pulls out of French Open.
Surprise package Davidovich Fokina, who knocked out top-ranked Novak Djokovic and Indian Wells champion Taylor Fritz in the earlier rounds at Monaco, drew first blood by breaking Tsitsipas to take a 2-1 lead in the opening set.
Sunday's final was an intense contest as nerves played their part, with 10 of the 22 games going against serve.
Rafael Nadal, the king of clay won his 11th French Open title on Sunday.
Rafael Nadal is chasing a historic 10th French Open title in Paris, but nothing will ever come close to trying to win his second.
Novak Djokovic has suffered more than his fair share of heartache against Rafael Nadal at the French Open but Sunday's final offers him a chance to dethrone the claycourt king.
World number one Novak Djokovic is on verge to become the first man to win US$100 million in prize money as he aims to book his place in the quarter-finals of the French Open for the 10th time.
The 20-year-old Korda, son of 1992 runner-up Petr, had enjoyed a dream run in his first Tour-level event on clay and was up against his idol -- the man he named his cat after.
Francesca Schiavone became the first Italian woman and the oldest first-time Grand Slam winner since 1969 when she won the French Open in 2010
Rafael Nadal is tied with Roger Federer as the player with the most men's singles majors and the Spaniard can now overtake his great rival who has skipped the Australian Open.
The moment Novak Djokovic accepted that being part of the Roger Federer/Rafael Nadal era was a chance, not a curse, everything improved for him.
The 20-times Grand Slam champion said he was having some "unpleasant moments" but was hoping to feel better soon.
The French Open tennis tournament has been postponed until September 20-October 4 amid the coronavirus outbreak, organisers of the season's second Grand Slam said on Tuesday. It was initially scheduled to be played from May 24-June 7.
Photos from the French Open matches played at the Roland Garros on Thursday
Images from Day 1 of the 2020 French Open, in Paris, on Sunday.
The unseeded Ostapenko, 20, downed Romanian third seed Simona Halep 4-6, 6-4, 6-3 in the final, hitting a staggering 54 winners and taking her tournament tally to 299.
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