The American overwhelmed 43rd-ranked Annika Beck of Germany 6-3, 6-0 in her third-round match on Centre Court at the All England Club in London.
The 34-year-old Williams moved past Chris Evert into second for career Slam victories in the Open era. Williams improved to 300-42 at major tournaments and trails only Martina Navratilova, who went 306-49 in her career.
"Oh gosh really?" Williams said with a laugh when a BBC commentator told her of the milestone. "I had no idea.
"That's awesome, right? That's good, right? I think that's a lot of matches."
Williams won the first three Grand Slams of 2015 but she has failed in her last three attempts to match Steffi Graf's Open era record of 22 major titles. Williams is now 82-10 at Wimbledon.
Williams, who has won six of her 21 Grand Slam titles at Wimbledon, compiled a 25-2 edge in winners against Beck.
Matches were played on Wimbledon's middle Sunday for only the fourth time in the tournament's 139-year history because of rain delays in the first week that caused a backlog.
"Obviously I love having that Sunday off, but I'm a little behind in my matches, so I guess I had to play an extra day," Williams said.
Williams fell an early break behind at 2-1 but won 11 of the final 12 games and 24 of the second set's 28 points.
"I still want to get out to a little bit of a faster start," Williams said. "But I was really focused and calm today."
Williams will next face two-time major champion Svetlana Kuznetsova of Russia, who rallied to beat American Sloane Stephens 6-7 (1), 6-2, 8-6.
No. 21 Anastasia Pavlyuchenkova of Russia reached the fourth round at Wimbledon for the first time, stopping No. 11 Timea Bacsinszky of Switzerland 6-3, 6-2.
Pavlyuchenkova will next face No. 27 American Coco Vandeweghe, who defeated No. 7 Roberta Vinci of Italy 6-3, 6-4.
"Roberta's a really tough opponent," said Vandeweghe, who is 4-0 against top-10 players this season. "She has a lot of craftiness to her game that you don't see too much. She makes you beat her. So that's what I tried to do, stay focused and keep pressing."
Elena Vesnina of Russia beat American qualifier Julia Boserup 7-5, 7-5 and Ekaterina Makarova of Russia defeated No. 24 Barbora Strycova of Czech Republic 6-4, 6-2.
On the men's side, American John Isner lost another marathon match at Wimbledon, losing 19-17 in the fifth set to Jo-Wilfried Tsonga of France in the third round.
Tsonga, seeded No. 12, came back after dropping the first two sets to outlast No. 18 Isner 6-7 (3), 3-6, 7-6 (5), 6-2, 19-17 for Tsonga in nearly 4 1/2 hours.
The 6-foot-10 Isner is best remembered for the monstrous match he won at Wimbledon six years ago against Nicolas Mahut that took three days and a total of 11 hours, 5 minutes and was decided 70-68 in the fifth set.
This time, Tsonga and Isner played their first three sets on Saturday before play was suspended because of darkness and then resumed Sunday.
Tsonga had to save a match point while serving and trailing 16-15 in the fifth and got the only break of the final set, which lasted more than two hours, to go ahead 18-17.
"It's good to be alive," Tsonga said.
The 31-year-old Isner had 38 aces and 101 winners, and Tsonga had 21 aces and 88 winners.
Isner was asked by reporters whether the 2010 marathon match flashed in his mind as the fifth set progressed.
"No," Isner said. "He was serving very well. I knew the match could go a long way. But I wasn't thinking about six years ago."
Tsonga will next face countryman No. 7 Richard Gasquet, who finished off a 2-6, 7-6 (5), 6-2, 6-3 victory over Albert Ramos-Vinolas of Spain.
No. 10 Tomas Berdych of Czech Republic beat No. 24 Alexander Zverev of Germany 6-3, 6-4, 4-6, 6-1 and Jiri Vesely of Czech Republic defeated No. 31 Joao Sousa of Portugal 6-2, 6-2, 7-5 in the third round.