Maria Sharapova's impressive sequence of French Open results ended when she was knocked out 7-6(3), 6-4 by 13th-seeded Czech Lucie Safarova in the fourth round on Monday.
The second-seeded defending champions had reached the previous three finals at Roland Garros, winning in 2012 and 2014, but could not handle her opponent's steely forehand.
Safarova, who had never progressed to the quarter-finals on the Paris clay in 10 previous attempts, hit 20 forehand winners to unsettle the former World No 1 on Court Philippe Chatrier.
She next faces 21st seed Garbine Muguruza after the Spaniard went through to the last eight for the second year in a row by defeating Italy's Flavia Pennetta in straight sets.
Sharapova, who had lost only one of her previous 24 matches at Roland Garros, dropped her serve in the third game but broke back in the eighth when her opponent double-faulted. She then lost her fourth consecutive tiebreak of the season.
The Russian, who has five Grand Slam titles to her name, went 3-0 down in the second set but fought back to 3-3 after Safarova made a mess of a routine forehand at the net with the court wide open. The Czech regained control and ended the contest on Sharapova's serve with a forehand winner.
Under-par Serena given a scare by Stephens
Serena Williams continued to struggle through the French Open draw, huffing and puffing her way into the quarter-finals with a 1-6, 7-5, 6-3 win over fellow-American Sloane Stephens.
Stephens broke serve three times in the opening set against the 2002 and 2013 champion.
Williams, the 19-times Grand Slam winner, broke serve twice in the second set to level.
Stephens then faded away as Williams broke for a 3-2 lead in the decider before finishing the match on Stephens' serve with a dipping crosscourt backhand winner.
She next faces 17th seed Sara Errani of Italy for a place in the semi-finals.
Williams, who hit 43 unforced errors, has had to work hard to make progress this year and labelled her performance unprofessional after defeating Germany's Anna-Lena Friedsam in the second round.
She also dropped the first set in the third round against former world number one Victoria Azarenka.
Muguruza repeats run to French Open quarters
Earlier, Spain's Muguruza proved last year's impressive performance at the French Open was no fluke when she repeated her run to the quarter-finals with a 6-3, 6-4 win over 28th-seeded Pennetta.
Muguruza broke decisively in the seventh game of the first set and rallied from 3-0 down in the second, the 21st seed's powerful ground strokes eventually becoming too hot to handle for Pennetta.
Despite a low first-serve percentage, the 21-year-old wrapped up the contest on her first match point when Pennetta coughed up an unforced error with a backhand.
Ruthless Ferrer too good for Cilic
Spaniard David Ferrer slipped almost unnoticed into the quarter-finals with a dismissive 6-2, 6-2, 6-4 win over Croatia's Marin Cilic.
The 33-year-old seventh seed was at his relentless best as he suffocated the more powerful Cilic, moving easily through to his sixth quarter-final at Roland Garros.
Ferrer, who lost to compatriot Rafael Nadal in the 2013 final, made only 14 unforced errors and Cilic simply did not have patience to grind it out, dropping serve five times.
Next up for Ferrer, one of only two Spaniards to reach the last 16, the lowest number since 1996, is either third seed Andy Murray or Frenchman Jeremy Chardy.
Federer dismisses Monfils to reach last eight
Roger Federer reached the quarter-finals with a 6-3, 4-6, 6-4, 6-1 defeat of local favourite Gael Monfils.
The match, resuming at one-set all on Court Philippe Chatrier after being held over from Sunday, began with the second-seeded Swiss breaking serve.
Federer, who had lost his two previous encounters against the 13th-seeded Frenchman, never looked back and went on to complete his fourth victory over Monfils at Roland Garros.
He next faces compatriot Stan Wawrinka, the eighth seed.
Nadal chalks up win number 70 at Roland Garros
Rafa Nadal warmed up for a possible quarter-final blockbuster against world number one Novak Djokovic with a 6-3, 6-1, 5-7, 6-2 triumph over American tyro Jack Sock.
The omens had looked rather foreboding for Sock even before he stepped on court for the fourth round encounter -- with his rival holding an 11-0 win-loss record against Americans on clay.
Sock's hopes of stalling that run looked all but over within the opening exchanges of the contest when he fell 3-0 behind to the nine-times champion.
The 22-year-old unexpectedly snatched the third set from Nadal but that only delayed the inevitable as the Spaniard became the first man to win a record 70 matches at Roland Garros when he fired down an unreturnable serve.
The Spanish sixth seed is bidding to become the first man to win 10 titles at the same grand slam.
Djokovic sets up Nadal clash
Djokovic demolished Frenchman Richard Gasquet 6-1, 6-2, 6-3 in an awe-inspiring performance to set up a much-anticipated quarter-final clash with Nadal.
The Serb needed seven break points to break the 20th seed's serve in the third game but once he had that advantage in the bag, there was no looking back. The top seed won nine games in a row to put Gasquet on the ropes.
Drop shots, gravity-defying crosscourt backhand winners and steely defence -- Djokovic had way too much in his reserves to sink a hapless Gasquet.
The French favourite managed to please the Court Philippe Chatrier crowd with some sublime one-handed backhands but they failed to stall Djokovic's charge towards the quarter-finals.
Djokovic, who dropped serve only once, ended Gasquet's ordeal with an exquisite dropshot as he continued his quest to win the only grand slam title missing from his collection.
Murray silences Chardy with racket work
Andy Murray let his racket, rather than his mouth, do the talking when he silenced Jeremy Chardy with a 6-4, 3-6, 6-3, 6-2 win in the fourth round.
The Frenchman was critical of Murray's decision to pull out of last month's Italian Open, citing exhaustion, after he had lost to the Scot in the second round.
"If you want to win a grand slam, everybody is tired," the Frenchman said. "So I was a little bit pissed when I saw he retired because of tiredness."
The Scot showed just what he was capable of producing on Monday following the extra rest he gave his body in the buildup to the claycourt major.
He next faces Spain's David Ferrer for a place in the semi-finals.