Svetlana Kuznetsova's hopes of a second US Open title were ended by in-form Serb Jelena Jankovic in the last 16.
Jankovic is through to her first Grand Slam quarter-final
The 2004 champion hit 41 winners but also made 46 errors and Jankovic's steadier play earned her a 6-7 (5-7) 6-3 6-2 victory over the sixth seed.
Jankovic, who beat Nicole Vaidisova in the previous round, will meet Russian Elena Dementieva in her first ever Grand Slam quarter-final on Wednesday.
Dementieva, the 2004 finalist, overcame French teenager Aravane Rezai 7-5 6-4.
"I never played her before and I was a bit afraid because she has nothing to lose," said Dementieva.
"She likes to hit the ball as hard as possible every single time, but sometimes you have to play safe."
In the same half of the draw, second seed Justine Henin-Hardenne demolished Israel's Shahar Peer for the loss of just one game.
The Belgian looked in daunting form as she won 6-0 6-1 in 50 minutes.
"It was a very good match for me," she said. "I did a lot of serve and volleying today and that helped me to stay aggressive."
She will next face 1998 champion Lindsay Davenport, who powered past seventh seed Patty Schnyder 6-4 6-4.
The American said she had surprised herself by getting to the quarter-finals.
Davenport missed nearly five months of the season with a back injury and then suffered a shoulder problem in the lead-up to the US Open.
"I'm ecstatic that I've gotten to this point," she said.
"I promise you if someone had asked me at Wimbledon, I would have laughed that I would even be able to play here. It's been amazing."
Maria Sharapova recovered from a slow start to beat China's Li Na 6-4 6-2 and reach the quarter-finals.
Li, the first Chinese woman to make the last 16 at Flushing Meadows, raced to a 4-1 lead but Sharapova hit back to wrap up victory in 78 minutes.
"I rushed into things. I rushed into my serve and my return. After 4-1, I kind of relaxed and just made her hit an extra ball," said the third seed.
The Russian will face Tatiana Golovin, who beat Anna Chakvetadze 6-3 6-2.