"I just rolled it. I don't know why," said Williams. "I was volleying and it just went over, so that was a little frustrating."
Add third-seeded Karolina Pliskova to the list of top women to fall at the U.S. Open.
Roger Federer has gotten his groove back.
Second-seeded Ash Barty is out of the U.S. Open, beaten 6-2, 6-4 by Wang Qiang, who advanced to a Grand Slam quarterfinal for the first time.
Coco Gauff's second Grand Slam tournament has ended with a 6-3, 6-0 loss to defending champion Naomi Osaka in the third round of the U.S. Open.
Marin Cilic won a battle of big servers, with a key service breaking helping him beat American John Isner 7-5, 3-6, 7-6 (6), 6-4 to advance to the U.S. Open's round of 16.
Rafael Nadal had no trouble downing qualifier Hyeon Chung 6-3, 6-4, 6-2 to reach the U.S. Open round of 16.
Bianca Andreescu used a steady baseline game to beat Caroline Wozniacki 6-4, 6-4 and advance to the U.S. Open round of 16.
Taylor Townsend keeps coming to the next and keeps winning, beating Sorana Cirstea 7-5, 6-2 to advance to the U.S. Open round of 16 for the first time.
There was no slow start to this U.S. Open outing for Roger Federer, who bristled at the suggestion that he might have played a role in some favorable scheduling.