Sakkari beat Swiatek to face Barbora Krejcikova of Czech Republic for a place in the semifinals when for the first time in Open era, the games will feature four women who have never previously got this far at the Slams.
Maria Sakkari has stunned defending champion Iga Swiatek to become the first Greek woman to reach a Grand Slam semi-final at the French Open as Novak Djokovic and Rafael Nadal closed in on another blockbuster clash.
World number 18 Sakkari triumphed 6-4, 6-4 over Polish eighth seed Swiatek and will face 33rd-ranked Barbora Krejcikova of the Czech Republic for a place in the final.
Thursday's other semi-final sees Russian 31st seed Anastasia Pavlyuchenkova tackle unseeded Tamara Zidansek of Slovenia.
For the first time in the Open era, the French Open semi-finals will feature four women who have never previously got this far at the Slams.
"I am speechless. It is a dream coming true. It's a very nice feeling and I could not have done it without my team and their support," said the 25-year-old Sakkari.
"We have a long way to go but we made a huge step today."
Swiatek had gone into the match on the back of 22 consecutive sets won at the French Open but her challenge was hobbled by a right thigh injury which needed taping during a medical timeout early in the second set.
Her defeat means that Justine Henin remains the last player to defend the women's title in Paris in 2007.
Greece will have two players in the semi-finals this year after Stefanos Tsitsipas made it to the last four on Tuesday.
Krejcikova knocked out American 17-year-old Coco Gauff 7-6 (8/6), 6-3 after saving five set points in the opener and then needing six match points to finish the job.
Gauff, the 24th seed and the youngest quarter-finalist at a major in 15 years, was undone by seven double faults and 41 unforced errors.
"I never really imagined I'd be standing here one day on this court, especially in singles, and being able to win," said Krejcikova, who had been so paralysed by fear before her last 16 victory over Sloane Stephens that she locked herself in a stadium office and wept.
Krejcikova, now on a 10-match winning streak, is having a busy week. She is also in the semi-finals of the women's doubles.
Djokovic, Nadal on collision course
Later on Wednesday, Nadal dropped a set at Roland Garros for the first time in two years but roared back to beat 10th seed Diego Schwartzman 6-3 4-6 6-4 6-0 and storm into the French Open semi-finals.
World number one Djokovic, the 2016 champion, and an 18-time Grand Slam title winner, is due to face Italian ninth seed Matteo Berrettini.
Victory would put the Serb into the semi-finals in Paris for the 11th time and only two wins away from becoming only the third man in history to win all four majors twice.
Djokovic had to dig deep against another Italian to guarantee his passage to a 15th quarter-final in Paris.
He was given a huge scare when 19-year-old Lorenzo Musetti raced into a two-set lead before running out of steam and quitting in the fifth.
"Berrettini has a big serve, big forehand. Two big weapons. He's in form," said Djokovic who defeated the Italian in their only previous meeting at the 2019 ATP Tour finals.
Djokovic will be into a 40th Grand Slam semi-final if he succeeds.
Berrettini has been solid on clay this year, finishing runner-up in Belgrade and Madrid but the highest-ranked player he has faced in Paris is world number 91 Kwon Soon-woo, his third round opponent.
He arrives fresher than Djokovic have been given a walkover into the last eight when Roger Federer withdrew from the tournament.
Meanwhile, the latest easing of Covid-19 restrictions in France from Wednesday and a later curfew from 11pm means a rise in the number of spectators at Roland Garros.
The final evening session of the tournament will have spectators for the first time with 5,000 fans able to watch the Djokovic-Berrettini quarter-final.