The world No.1 had a much tougher time of it against Varvara Lepchenko than she had against either Taylor Townsend or Vania King but was ultimately a convincing 6-3, 6-3 winner in breezy conditions.
Lepchenko, who is of Uzbek descent, had not won more than two games in a set against Williams in their two previous meetings. She was also looking to become only the second left-handed player after Ekaterina Makarova to beat Williams at a grand slam. The world No.1 has shown tunnel vision so far this tournament after her slam wobbles this season and quickly moved into a 3-1 lead. Lepchenko fought back to level with some terrific play but could not prevent Williams pulling away to take the opening set.
The second was a real battle but Williams won the points that mattered, holding off break points in the fifth game and then forging ahead for 4-3.
That proved the crucial stage of the match and Williams clinched victory after an hour and 35 minutes when Lepchenko netted a backhand.
The two-time defending champion next plays Estonian Kaia Kanepi, who upset 15th seed Carla Suarez Navarro 7-5, 6-0.
Maria Sharapova overcame Sabine Lisicki to set up a tasty fourth-round clash with Caroline Wozniacki.
There was nothing pretty or straightforward about Sharapova’s 6-2, 6-4 victory, which took an hour and 41 minutes late on Friday night, but she was the tougher in the end under the lights on the Arthur Ashe Stadium court.
Lisicki had only won one of six previous meetings against Sharapova, at Wimbledon in 2012, but her big game means she is always a danger.
Sharapova said: “She was a really tough opponent, a very aggressive, big server. I just tried to concentrate on my return. I wasn’t serving as well as I wanted to.
“In the end it was a few points. I was happy I was able to break her.”
Sharapova added she was hoping for a “goodnight hug” from boyfriend Grigor Dimitrov, who won his second-round match earlier.
Wozniacki has had an impressive summer and was very solid in a 6-3, 6-2 victory over 18th seed Andrea Petkovic.
“I think every match I get into a better groove out there and I’m playing better,” said the Dane.