Nadal, bidding for a record-extending 14th French Open title, won the first five games of the match as he looked on course to repeat his drubbing of the Serb in last year's final.
Iga Swiatek, who beat American teenager Coco Gauff 6-1, 6-3 in Saturday's final at Roland Garros, went from being a largely unknown 19-year-old, ranked 54th in the world, to instant celebrity status after lifting her first Suzanne Lenglen Cup 18 months ago.
Djokovic's challenger will be a 22-year-old who is bidding to become the first Greek to win a singles major.
Thiem knocked out by Andujar in French Open first round
Novak Djokovic kept his bid alive for Grand Slam No. 23 as he entered the semifinals of the French Open.
Images from Day 8 of the 2021 French Open at Roland Garros in Paris on Sunday
IMAGES from Day 8 of the French Open, at Roland Garros, on Sunday.
Djokovic is the first man to reach 10 successive quarter-finals at the French Open
Images from Day 9 at the French Open.
A summary of Thursday's play at the French Open.
IMAGES from matches on Day 8 at the French Open
Rafael Nadal returns to his favourite tournament, albeit not his preferred court, to begin pursuit of a record-extending 10th French Open title on Monday against Frenchman Benoit Paire.
Tournament favourite Novak Djokovic beat Finnish veteran Jarkko Nieminen 6-2, 7-5, 6-2 on Tuesday, kicking off his quest for a first ever Paris trophy to add to his eight other Grand Slams.
What happened on Day 3 of the French Open was more surprising. Two of the top five seeded women exited.
Two-time Grand Slam winner Victoria Azarenka crashed out of the French Open in the first round losing 5-7, 5-7 to Katerina Siniakova on Monday, playing only her fifth tournament of the year after a legal battle over the custody of her son.
No one will be able to match up to his iconic sense of style!
The 20-year-old Ostapenko was the first unseeded woman to lift the Suzanne Lenglen Cup since Britain's Margaret Scriven in 1933.
Czech fourth seed Tomas Berdych bulldozed his way into the second round of the French Open by thrashing Japanese qualifier Yoshihito Nishioka 6-0, 7-5, 6-3 on Monday.
Nadal stretched his record of men's singles Grand Slam titles to 22
The Spaniard, who turns 36 next week, will next meet Dutch 26th seed Botic van de Zandschulp with a potential quarter-final looming against world number one Novak Djokovic who defeated him in last year's semi-finals.
American Bethanie Mattek-Sands and the Czech Republic's Lucie Safarova claimed their third consecutive grand slam doubles title with a convincing 6-2, 6-1 victory over Australian duo Ashleigh Barty and Casey Dellacqua at the French Open on Sunday.
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.
Images from Day 6 of the 2021 French Open at Roland Garros in Paris on Friday.
The two great rivals meet at Roland Garros for the first time in eight years in Friday's tie.
A summary of the matches from Day 9 at the French Open.
Sunday's final was an intense contest as nerves played their part, with 10 of the 22 games going against serve.
Images from Day 13 of the French Open, at Roland Garros, in Paris.
Images from Day 12 of the 2021 French Open at Roland Garros in Paris on Thursday.
IMAGES from Day 6 of the French Open at Roland Garros in Paris on Friday.
The 20-times Grand Slam champion suggested after the third-round clash which ended past midnight that he could preserve himself for Wimbledon which begins on June 28.
Images from Monday's action at the French Open.
Garbine Muguruza's chances of winning her maiden grand slam title -- and achieving the rare feat of beating Serena Williams twice in three years at Roland Garros -- may well depend on which version of the world number one turns up on Sunday.
Images from Day 6 at the French Open, at Roland Garros, in Paris, on Friday.
Stanislas Wawrinka trumped fellow Swiss Roger Federer at a grand slam for the first time with a 6-4, 6-3, 7-6(4) victory in the French Open quarter-finals on Tuesday.
'You can't be frustrated all the time because the neighbour has a bigger house than you, or a bigger TV or better garden. That's not the way that I see the life, you know'
Barbora Krejcikova claimed her maiden Grand Slam title when she beat Russian Anastasia Pavlyuchenkova
IMAGES from Day 9 of the French Open at Roland Garros in Paris on Monday.
Russia's Anastasia Pavlyuchenkova stands on the threshold of finally delivering the title long predicted
'I will put everything I have Saturday on the court'
Even the Parisian stormclouds cleared for Serena Williams on Tuesday, as the new mother's baby steps back to Grand Slam tennis became a stride into the second round of the French Open.