The 17th-ranked Russian pressured Williams’ backhand, the same tactic that worked a day earlier in an upset of top-ranked Justine Henin.
“It’s not like I played my best and lost, it could be worse,” Williams said. “I can sit here and name 50 things I could do better.”
Safina will face 18-year-old Victoria Azarenka of Belarus in Saturday’s semifinals. Azarenka ousted 15th-seeded Alona Bondarenko 7-6 (2), 6-2.
Elena Dementieva downed Jelena Jankovic 6-3, 2-6, 6-3 to reach the other semifinal. She will face either Ana Ivanovic or Agnes Szavay, who split 3-6, 6-4 before the match was postponed because of darkness.
Dementieva faces the winner in Saturday’s semifinals, while Safina plays Victoria Azarenka, an 18-year-old who ousted 15th-seeded Alona Bondarenko 7-6 (2), 6-2.
Williams was chasing a fourth straight title and appeared poised to improve to 21-1 this year until Safina’s hard shots began to land in the second set. In the deciding tiebreaker, Williams let a 4-3 lead slip away and sent a forehand long and wide to end the match.
“I couldn’t concentrate, I started the match like, ’I won yesterday,’ so that was good,” Safina said. “Then I started believing I could win. I just had to be more aggressive.”
Williams was the 10th top-10 victim for Safina, the 22-year-old sister of two-time grand slam champion Marat Safin. Safina slumped in 2007 and said a victory last month against Lindsay Davenport at the Sony Ericsson Open restored her belief in her ability to beat top players.
Safina said her brother sent a “Roll on, sister” message after the win against Henin, a four-time French Open champion.
Even though she’s defeated top players, including Maria Sharapova, the Russian didn’t see herself among their ranks.
“I’m No. 17. It’s such a long way,” Safina said. “How far I can go?”
When Safina raised her game in the second set, she broke serve twice, whipping a shot past Williams at the net to take a 4-0 lead.
“I think she’s playing far better than in the past,” Williams said.
With the many upsets at the German Open, Williams said it will be hard to name a favorite for June’s French Open.
“I’m excited I lost here and not in Roland Garros,” Williams said. “The pressure is off me.”
ALSO ON THIS STORY Discuss: Sound off on tennis message boards