Francesca Schiavone, the 2010 French Open champion, tumbled out of Roland Garros and the world top 20 on Saturday in a marathon three-hour, three-set loss to unseeded American Varvara Lepchenko.
Italian 14th seed Schiavone, who was also runner-up to Li Na in 2011 and the oldest woman left in the tourament, lost 3-6, 6-3, 8-6 to Lepchenko, the world number 63 who has now reached the last 16 of a Grand Slam for the first time.
The Uzbekistan-born left-hander also provided another timely boost for American women's tennis which was sent reeling by the shock first loss of Serena Williams and the more predictable second round exit of Venus Williams.
Sloane Stephens had reached the fourth round on Friday while Christina McHale can make it three Americans in the last 16 if she gets past Li Na.
Lepchenko squandered the opportunity to serve for the match against the 30-year-old Schiavone in the ninth game of the decider, but held her nerve in the 14th game to take the tie.
It was the 26-year-old Pennsylvania-based player's second successive win over Schiavone, having also won in three sets in the second round of the Madrid claycourt tournament in May.
Wimbledon champion Kvitova struggled past Russia's world number 109 Nina Bratchikova 6-2, 4-6, 6-1 to reach the last 16 for the third time.
The 22-year-old served up eight double faults and committed 37 unforced errors and was only saved by the fierce, flat hitting of her groundstrokes which often left the Portugal-based Bratchikova gasping.
"I started well, had a set already, and then I was very aggressive and I knew what I had to do," said Kvitova.
"In the second set I was still like, okay, if I play like the first set, it will be fine. But it wasn't. She played much better than the first set. She had a better serve, and it was tough to return," admitted Kvitova.
"She had pressure from the first shot that she played. I was running side to side and that's not my game. So I had to change and be aggressive and put her a little further back."
Also making the last 16 was Kazakh qualifier Yaroslava Shvedova, a quarter-finalist in 2010, who eased past Spain's Carla Suarez-Navarro 6-4, 7-5.
Shvedova will tackle either Li, the seventh seed, or McHale for a place in the last eight.
Later on Saturday, second seed Maria Sharapova, who needs a French Open title to complete a career Grand Slam, faces Chinese 28th seed Peng Shuai, defending a 3-1 career record aganst the 26-year-old from Tianjin.
Former world number one Caroline Wozniacki, the ninth seed, meets Kaia Kanepi of Estonia.