The prospect of two 36-year-olds winning at the All England Club ended after defending men's champion Federer's shock five-set defeat to Kevin Anderson.
But on Thursday Williams faces Julia Goerges of Germany for a place in the women's final, in only her fourth tournament since the birth of her daughter Olympia.
She is 1/4 to reach the final with Goerges 3/1 to spring a Centre Court surprise.
Goerges' success is all the more surprising because she had lost in the first round for the last five years at Wimbledon and considered grass her weakest surface.
"For me it's much sweeter to get to the semi-final here than in probably other grand slams because I didn't expect it," she said.
For Goerges to make it one step further she must do what no player has done since Alize Cornet in 2014 - beat Williams in singles at Wimbledon.
The 13th seed added: "Obviously she has won so many titles here, not only here, a lot of grand slams beside Wimbledon. It's an honour to share the court with her."
In the other women's semi-final Angelique Kerber meets last year's French Open champion Jelena Ostapenko. She is 4/7 to reach the final with Ostapenko 11/8.
Federer vowed to return to Wimbledon next year after a shock quarter-final defeat to Kevin Anderson denied him the chance of a ninth title.
Rafael Nadal and Novak Djokovic will contest a blockbuster semi-final while eighth seed Anderson will face fellow big server John Isner, seeded ninth, for a place in the final.
Defending champion Federer was two sets up and had a match point in the third, but almost three hours later he trudged off on the end of a seismic 2-6 6-7 (5/7) 7-5 6-4 13-11 upset.
Federer said: "Of course the goal is to come back here next year. I wouldn't call it 'unfinished business'. I felt like I did some good business here in the past already "So I'm all right. I'm just disappointed now."
Nadal, the world number one and second seed, came through a memorable Centre Court battle against Juan Martin Del Potro 7-5, 6-7 (7/9), 4-6, 6-4, 6-4.
Djokovic, seeded 12th, beat Kei Nishikori 6-3 3-6 6-2 6-2 while Isner sank Milos Raonic 6-7 (5/7) 7-6 (9/7) 6-4 6-3.
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