The 36-year-old American moved safely into the fourth round after a tough 7-5 7-6 (7/2) win over Kristina Mladenovic on Centre Court.
But while the 23-time grand slam winner made it through to the second week, at least eight of the top 10 seeds will be absent.
Friday’s casualties were Serena’s sister Venus, who saw her hopes of winning a sixth title halted by Dutchwoman Kiki Bertens in a Court One marathon, and fellow American Madison Keys.
Serena, seeded 25th and playing her first Wimbledon since becoming a mother last year, said: “I think a lot of the top players are losing, but they’re losing to girls that are playing outstanding.
“I think, if anything, it shows me every moment that I can’t underestimate any of these ladies. They are just going out there swinging and playing for broke.”
Ninth seed Venus had battled back from a set and a break down to haul herself level against Bertens.
And Bertens, seeded 20th, had to call on all her reserves of energy to see off 38-year-old Venus 6-2 6-7 (5/7) 8-6 in a match lasting two hours and 40 minutes.
Venus said: “I just ran out of time in the end. She played really well, you have to win the last point and I didn’t succeed in that.
“I think she was a little bit luckier than I was in the end. Sometimes it takes luck and skill and she definitely deserved to win.”
When asked if she would be back at the championships next year, Venus said: “Yeah.”
Keys, the 10th seed and last year’s US Open winner, bowed out to Russian world No 120 Evgeniya Rodina.
After an agonising 7-5 5-7 6-4 defeat, the 23-year-old Keys admitted the prospect of a fourth-round meeting with Serena was playing on her mind.
“It was like, ‘so if you win, then you play this person’. And I think that kept being in the back of my mind,” Keys said.
“I think that’s something that with experience I have to be able to completely push aside and not think about. But I don’t think I did a great job of that today.”
Czech Karolina Pliskova narrowly avoided the cull of the top seeds when she came from a set down to beat Mihaela Buzarnescu.
The seventh seed took the second set on a tie-break and it proved pivotal as she ran out 3-6 7-6 (7/3) 6-1 winner.
Pliskova will meet Bertens in the fourth round.
Ekaterina Makarova, who knocked out second seed Caroline Wozniacki on Wednesday, maintained her fine run with a 4-6 6-4 6-1 win over Czech Lucie Safarova.
The Russian will face Italy’s Camila Giorgi, who came from a set down to beat Czech Katerina Siniakova.
Donna Vekic of Croatia swept aside Belgium’s Yanina Wickmayer in straight sets and will meet Germany’s Julia Goerges, a 7-6 (7/3) 3-6 10-8 winner over Barbora Strycova of the Czech Republic.
Simona Halep, the world No 1 and, alongside Pliskova the only other top 10 seed still in the draw, faces Taiwan’s Hsieh Su-wei on Saturday.