The former British number one believes there is every chance of a maiden Grand Slam winner in Roland Garros, where both three-time champion Williams, who is currently pregnant, and two-time winner Maria Sharapova – not awarded a wild card after her doping ban - will be absent.
Between them, the pair have won four of the last five titles in Paris and with defending champion Garbine Muguruza struggling for both form and fitness, Rusedski feels a new name could be on the trophy come June 10.
“There will be many players champing at the bit with no Serena there this year," the Eurosport pundit told sportinglife.com.
“Somebody who has never won a Slam before could win it – like (Rome winner) Elina Svitolina.
“Many must be thinking, with Serena out for a little while, ‘this is my chance to take advantage’.”
Simona Halep is the current favourite with the bookies but she is nursing an ankle injury sustained in her Italian Open defeat in Rome and described her chances of lining up in Paris as only “50-50” on Wednesday.
That could see the in-form Svitolina go off as favourite despite the fact that in her 18 previous Grand Slam appearances only once has she been beyond the last 16.
Rusedski added: “It’s one of the most wide-open draws going into the French Open I can remember.
“Muguruza won last year but hasn’t been exceptional.
“Halep has an injury cloud over her after she tweaked her ankle.
“I don’t actually have one choice (for a potential winner). If Halep didn’t twist her ankle I would have made her favourite from the formlines but there are so many possibilities, especially with no Serena.
“I think there could be a massive surprise, like when Francesca Schiavone won (in 2010).
“I think the women’s event will really play into a good tournament – it will be just as exciting as the men’s. In the men’s there are probably three to five potential winners – in the women’s it’s as many as 10.”
Is Briton Johanna Konta among them?
Rusedski responded: “She’s got a chance but struggles a bit with the movement on the clay. She’s not a natural slider on it.
“Her coach (Wim Fissette) has been with a lot of top players – Victoria Azarenka, Kim Clijsters - and you can see she’s getting better on the clay if you look at the subtleties.
“She can build on that and improve the way she moves.”
Click here for Rusedski on Andy Murray's chances
Click here for Rusedski on the Djokovic-Agassi link-up
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