Williams's triple century moved the world number one above Chris Evert into sole ownership of second place in the all-time list, with only Martina Navratilova's Open era record of 306 ahead of her.
Serena Williams has now won 82 matches at Wimbledon as she remains on course to equal Steffi Graf's Open era record of 22 Grand Slam titles with her seventh Wimbledon crown.
She was in peak form on Centre Court, hitting 25 winners and seven aces as she took just 51 minutes to set up a last 16 clash with Russian 13th seed Svetlana Kuznetsova.
"Oh, was it? Cool. Oh, nice. I had no idea. That's awesome, right? I think that's a lot of matches. It's a lot of wins," Williams said when told of her landmark.
"I thought it was good. I still want to get out to a little bit of a faster start but I was really focused and calm.
"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."