And the number of remaining top-10 seeds is down to two after No. 9 Venus and No. 10 Madison Keys - beaten 7-5, 5-7, 6-4 Friday by Evgeniya Rodina, a qualifier ranked only 120th - were sent home.
Five-time champion Venus Williams did better with her comeback attempt. The eight-time champion Roger Federer shared a video where he said: '[The] first day at Wimbledon, just walking past court 18, still my favourite match [John] Isner against [Nicolas] Mahut, I still wish it was going on.
"Yeah, I'm very happy on both ends, absolutely", Federer said.
"I feel guilty if I take 15 minutes for myself to stretch". It was the sort of performance that would have endangered many elite players, yet it barely broke Williams's stride.
"I don't know. I don't know", he began, before offering quite a list for someone who doesn't know. And in between, Serena Williams, recently returned from maternity leave, underlined why she remains the mother of all champions.
"Obviously, in the last nine, 10 years now, since we have had children, I've been trying to make that work in some shape or form with my wife".
In this picture, Switzerland's Federer reacts after winning against Slovakia's Lukas Lacko during their men's singles second round match on the third day of the 2018 Wimbledon Championships at The All England Lawn Tennis Club on July 4, 2018, in Wimbledon, southwest London. "I hope I can win a few more matches here and the German crowd can watch some tennis". I feel sorry for her, because she's a very nice girl and friend.
"I think we have come through it well". Making her 21st Wimbledon appearance, 38-year-old Venus is the oldest woman in this year's tournament.
"I am happy how I am hitting the ball, good concentration on my service games and I'm able to mix it up with some slices and coming over on returns".
After dropping her first set to Romania's Alexandra Gulgheru, No. 9-seeded Williams bounced back strong to take two decisive back-to-back sets and move on.
Greek teenager Stefanos Tsitsipas struck 25 winners in a clinical display to beat Italian Thomas Fabbiano 6-2 6-1 6-4.
The seven-time champion's life is still a blur of nappies and interrupted sleep, but that didn't stop her grinding out a 7-5, 6-3 win over Holland's Arantxa Rus in the first round.
Romanian 29th seed Mihaela Buzarnescu thrashed British teenager Katie Swan, 6-0, 6-3 to extend her remarkable renaissance.