Belarussian Azarenka was beaten 6-2 7-6 by Slovakian 15th seed Dominika Cibulkova and must wait to see if Russian Maria Sharapova will claim the top spot.
Sharapova, who meets unseeded Czech Klara Zakopalova in the last 16 on Monday and has yet to drop a set here, must get to the Roland Garros final for the first time to become number one.
Cibulkova, who reached the French semi-finals three years ago and had lost seven times to Azarenka in eight previous meetings, collapsed on to her back, a big grin on her face, after winning the tiebreak 7-4 with a backhand crosscourt on her second matchpoint.
The Slovakian will play either U.S. Open champion Samantha Stosur of Australia or American teenager Sloane Stephens in the quarter-finals.
Asked by a reporter how she would recover from the defeat, a stone-faced Azarenka said sarcastically: "I'm going to kill myself!"
Azarenka, who had come within five points of defeat in the first round against Italy's Alberta Brianti, was also asked what had gone wrong on Sunday.
"Pretty much everything, really," she said. "I don't know how to describe my performance today...I wasn't satisfied being out there playing that way but I guess it happens."
Djokovic, the men's world number one, had to come back from two sets down to beat Italian Andreas Seppi and continue his quest to hold all four grand-slam titles at once.
DJOKOVIC ERRORS
The Serbian hit 77 unforced errors - 26 more than defending champion Rafa Nadal had racked up in three matches - before turning things around and managing to beat Seppi 4-6 6-7 6-3 7-5 6-3.
He will now play either fifth-seeded Frenchman Jo-Wilfried Tsonga or number 18 Stanislas Wawrinka of Switzerland.
Italy's Sara Errani saw off her second French Open champion in two rounds when she beat Russian Svetlana Kuznetsova 6-0 7-5 to reach the quarter-finals of the claycourt grand slam for the first time.
"I am curious to see how far I can go, what level I can get to," said clay specialist Errani, who had knocked out Serbian Ana Ivanovic, the 2008 winner, in the third round.
Kuznetsova's demise left Li Na as the only French Open champio n still in the women's draw, after earlier-round defeats for Francesca Schiavone and Serena Williams.
China's Li, who won last year, meets Kazakh qualifier Yaroslava Shvedova in the fourth round on Monday.
Sunday's matches were played under cloudy skies and Kuznetsova, who won in 2009, said the gloomy weather had affected her.
"Today the weather was so bad. I felt cold during the whole match. For me to move was really complicated, I couldn't make my feet move," said the Russian who started working with Marat Safin's old coach Hernan Gumy a week before the tournament.
Errani will now play another first-time quarter-finalist here, 10th seed Angelique Kerber who beat Croatian Petra Martic 6-3 7-5 on Suzanne Lenglen Court.
The Italian said she would change her tactics to play left-hander Kerber b ut, pressed on what she would do, told reporters with a smile: "I am not telling you for now, I am keeping it to myself."
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