The actress, 45, who previously starred in Trainspotting and is currently gracing screens as suspected bent copper DCI Joanne Davidson in the BBC cop drama, has shot up as the hot favourite to take on the role.
Her odds are currently 12/1 in the betting to next become the Doctor in the iconic franchise.
Death In Paradise star Kris Marshall and I May Destroy You writer and actress Michaela Coel also continue to head up the betting at 6/1 apiece.
Meanwhile, others featured on the list include Richard Ayoade and Michael Sheen.
Alex Apati of Ladbrokes said: "The race to replace Jodie Whittaker is more wide-open than it's ever been and Line Of Duty fans will be pleased to see Kelly Macdonald's odds have tumbled substantially over the past few weeks."
While there has been lots of chatter about Whittaker stepping down from her role as the Doctor, after taking up the role back in 2018, this is yet to be officially confirmed by the BBC.
The news was first broken by The Mirror at the start of this year, but no word from Jodie or the show followed.
Most of the actress' predecessors averaged three years in their roles, so it wouldn't be far fetched to assume the hunt for her replacement is now on.
An insider reportedly told the publication: "It's all very hush-hush but it is known on set that Jodie is leaving and they are gearing up for a regeneration.
"Her departure is top secret but at some point over the coming months the arrival of the 14th Doctor will need to be filmed. It's very exciting."
While Jodie is expected to leave her role alongside Bradley Walsh and Tosin Cole, showrunner Chris Chibnall is expected to remain.
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