Together, they have a huge 43 Grand Slam titles with rivals such as Rafael Nadal, Novak Djokovic, Venus Williams and Maria Sharapova often left trailing in their wake.
Fans have pined for the duo to face off in a one-off encounter over the years but Federer and Williams have so far resisted urges to do so.
But according to tennis fan Aleksa Milovanovic, writing on Quora in a post that has received over 100 upvotes, Serena would toil.
And he backed it up with a historical run-dow of previous encounters between men and women.
“This is what’s known as a Battle of the Sexes,” he wrote.
“In 1973, a retired 55-year-old Bobby Riggs defeated the imperious Margaret Court 6–2, 6–1.
“Bille Jean King asked for a rematch. Riggs accepted and lost in a best-of-5 match in 3 sets.
“That was a long retired, alcoholic smoker who challenged the 2 best players of the time to a tennis match.
“Later, Jimmy Connors and Martina Navratilova had a match. Navratilova was allowed to hit the doubles alleys and Connors was allowed only 1 serve. Connors won 7–5, 6–2.
“Finally, in 2003, Karsten Brasch challenged the Williams sisters after they stated they could defeat any men’s player ranked outside the top 200.
“Ranked 203, Brasch challenged them. They accepted.
Roger Federer and Serena Williams pictured back in 2009
“The sisters then claimed, after the loss, that they could beat any man ranked outside the world’s top 350. Brasch disagreed- saying ‘500 and above, no chance.’
“All this is to say, Roger Federer is the greatest men’s tennis player ever. He isn’t anything like Riggs or Brasch- he has some of the best training regiments that anyone could ask for.
“His strokes are imperious and he hits powerfully. Williams was unable to beat Brasch- or even make it competitive. How on earth would she fare against Roger Federer?
“My guess is she’d be very lucky to win a game in best of 5, and she’d probably win less than 20 points.”