And for the third match in a row, almost as though this was the plan all along, Williams righted herself to pull out a victory.
In a riveting, two-hour showdown between the last two American women in the draw, the No. 1-ranked and No. 1-seeded Williams was a game away from defeat Monday, then came back to beat Sloane Stephens, 1-6, 7-5, 6-3.
Williams reached the quarterfinals and avoided joining defending champion Maria Sharapova on the way out of Roland Garros.
"It's not how you start, I guess, it's how you finish," Williams said. "That's kind of how I'm looking at it."
Close as it was, thanks in large part to Williams' 43 unforced errors, more than twice as many as Stephens' 21, the eventual outcome seemed certain once Williams pulled even by taking the second set.
That's because she is 10-0 in three-setters this season.
The 1999 U.S. Open, when she collected her first major title, is the only other time Williams came back to win three straight matches after losing the first set, according to the WTA.
"There's a reason why she's the No. 1 player in the world," said Stephens, defeated in the French Open's fourth round for the fourth consecutive year.
Either Williams, in 2013, or Sharapova, in 2012 and 2014, has won the French Open the last three years. Only Williams has a chance to do it again Saturday because the second-seeded Sharapova was outplayed throughout a 7-6 (3), 6-4 loss to 13th-seeded Lucie Safarova.
"My opponent had a different gear than I did," Sharapova said after her earliest exit at Roland Garros since 2010.
Sharapova did not use the cold she's been dealing with as an excuse, saying: "I don't like to talk about it, and I don't think it really makes a difference."
In her first French Open quarterfinal, Safarova will face No. 21 Garbine Muguruza of Spain, who beat No. 28 Flavia Pennetta of Italy, 6-3, 6-4.
On a day full of tennis' biggest names, the Big 4 of the men's game — Roger Federer, Novak Djokovic, Rafael Nadal and Andy Murray — all won. The top-seeded Djokovic and nine-time French Open champion Nadal will play in the quarterfinals Wednesday, a rematch of last year's final.
Nadal eliminated the last U.S. man, Jack Sock, 6-3, 6-1, 5-7, 6-2, while Djokovic had no trouble in a 6-1, 6-2, 6-3 win over Richard Gasquet.
Federer needed about an hour to finish his 6-3, 4-6, 6-4, 6-1 victory over Gael Monfils in a match suspended because of darkness after the second set Sunday. Federer next faces Swiss Davis Cup teammate Stan Wawrinka, and Murray will play 2013 French Open runner-up David Ferrer.
Williams' quarterfinal opponent is 2012 runner-up Sara Errani, a 6-2, 6-2 winner over Julia Goerges.
The winner of Williams-Errani will go up against someone making her Grand Slam semifinal debut, because it will either be 23rd-seeded Timea Bacsinszky of Switzerland — who surprised two-time Wimbledon champion Petra Kvitova, 2-6, 6-0, 6-3 — or 100th-ranked Alison Van Uytvanck of Belgium.
The 40th-ranked Stephens, who is 22, knew she could compete with the 33-year-old Williams, having defeated her in the 2013 Australian Open quarterfinals.
Before taking the court Monday, Stephens shared a moment in the hallway with her coach, Nick Saviano. They bumped fists, and he patted her on the right shoulder.
When play began, Stephens won the first two games without the benefit of a single winner. Williams kept right on missing, much as she did early against 105th-ranked Anna-Lena Friedsam in the second round and former No. 1 Victoria Azarenka in the third.
"I feel like I'm living on the edge," Williams said. "But, you know, I've got to get off the edge."
After one forehand landed in the net, she looked down at the ground and said, "Oh, no." After another did the same, she let out an "Aaaaah!" of despair. A later miscue prompted Williams to twirl her racket overhead, as if to mock her poor swing.
Stephens led, 5-4, in the second set, a game from victory. From there, Williams won nine of the final 12 games.
"I don't really like to live like this," Williams said. "Believe me, I'm thinking, 'OK, Serena, pull yourself together.' "