But she recovered from a slow start Saturday and won Wimbledon for the second straight year, beating an ailing Venus Williams 4-6, 6-4, 6-2.
Venus played despite an abdominal strain she aggravated in the semifinals.
"I had to tell myself to look at the ball and nothing else," Serena said. "It's really tough. It shows what a great champion Venus is. She's really inspiring for me."
Venus didn't practice Friday, and two hours before the final she warmed up for only 10 minutes before limping off the court, raising fears she might not play.
But she did — and after one set she led.
"I came out here because I thought the people, the fans, deserved a final," Venus told the crowd during the trophy ceremony.
With the victory, however hollow, top-ranked Serena Williams has won five of the past six Grand Slam titles, giving her six career major titles. She has beaten her sister six times in a row, with the past five wins in Grand Slam finals, including two at Wimbledon.
Each match has been emotionally draining for the sisters, and this one was no different.
For the first hour, Venus appeared largely uninhibited by the injury, which has bothered her off and on for two months. She chased down shots in the corners, smacked crosscourt winners and hit her serve at up to 110 mph.
But the velocity of her serves gradually fell off, and as she hit one early in the third set, she clutched her side and grimaced. She lost the point and game to fall behind 1-0, then called for a trainer and left the court to have the tape around her abdomen adjusted.
She returned seven minutes later to a big ovation, and her first shot was a forehand return for a winner. But her next four returns were errant, putting Serena ahead 2-0.
Venus twice held serve to stay in the set. But she double-faulted, hunching over in pain on her follow through, to fall behind 5-2, and Serena served out the victory.
When Venus hit a return long on match point, she walked to the net and embraced her younger sister. As Serena waved and blew kisses to the crowd, Venus sagged in her chair, exhaled and managed a smile.
"It tugged at my heartstrings watching Venus out there," said their mother, Oracene Price. "I didn't want her out there in the first place, but that's her choice. That's what probably made it difficult for Serena at the beginning."
Awaiting the trophy presentation, the two sat side by side and shared a laugh. Venus then took a camera from her bag and asked an official to snap their picture.
Venus has won four major titles, but none since beating Serena in the first all-Williams Grand Slam final at the 2001 U.S. Open. The family has won four consecutive titles at Wimbledon — Venus was the champion in 2000 and 2001.
The men's final Sunday features No. 4-seeded Roger Federer against unseeded Mark Philippoussis, with each playing for his first Grand Slam title.
Venus had pledged "to at least show up" for the final, and she did. A bandage was visible under her corset dress, and her upper left leg was wrapped.
As always, the close sibling relationship made the dynamics of the match awkward. Serena, who consoled her rattled sister regarding the injury during a rain break in the semifinals, played at first as if distracted by worries about Venus' health.
"It was difficult," Serena said. "I didn't want her to be in any pain."
After losing two of the first three points, Venus ran off 11 in a row, breaking serve to take a 3-0 lead. Serena, accurate and overpowering in a semifinal victory over Justine Henin-Hardenne, found herself struggling to keep the ball in the court.
When she hit a backhand into the net in the fourth game, she tossed her racket in frustration. When she did it again to make the score 1-1 in the second set, she stooped over in anger and screamed, "Come on!"
Venus closed the first set by winning a wild 16-shot rally. Serena had a chance to hit an easy overhead putaway, but she appeared to freeze and instead merely popped the ball back. Then she tried a drop shot and it floated wide, giving Venus the point — and the set.
"I just wish it was one set instead of two out of three," Venus said.
Many exchanges found neither player at her best. Serena hit a 67 mph second serve, far off her norm, but Venus dumped a return in the net. Serena finished with 30 unforced errors to 25 for Venus.
Serena played 17 minutes before winning a game. But in the second set her play improved, while Venus began to move less swiftly and hit more stiffly. She lost four consecutive games to fall behind 5-1 and rallied briefly before Serena served out the set to even the match.
Serena received $960,250 and won for the seventh time in their 12 meetings. In every previous match, the sister that won the opening set won the match.
Venus received $446,725.