The 48-year-old actor's odds have shortened dramatically in the last 24 hours since Smith's departure from the show was confirmed by the BBC.
The Merlin and Law & Order: UK star has odds of 6/1 with SkyBet and is closely followed by Chiwetel Ejiofor at 7/1.
Being Human's Damien Molony follows with odds of 9/1.
Homeland star David Harewood and Russell Tovey both have odds of 10/1 with the bookmaker.
Matt Smith will leave the iconic role after this year's Christmas special. Companion Jenna Louise Coleman will continue to star alongside the new Doctor in 2014.
The 30-year-old said that it has been "an honour" to be a part of the long-running series.
Paterson Joseph - who was widely tipped to be David Tennant's replacement in 2010 - has odds of 16/1, while Tennant himself has odds of 33/1 for a return to the role.
> 'Doctor Who' Matt Smith departs - Who should play the Twelfth Time Lord?
> 'Doctor Who': Who won't be playing the Twelfth Doctor?
It was reported earlier today (June 2) that producers are considering a female star to play The Doctor. Broadchurch star Olivia Colman is the female favourite at 25/1.
Executive producer Steven Moffat teased the casting of the 12th Doctor, saying: "A life is going to change, and Doctor Who will be born all over again. After 50 years, that's still so exciting."
Harry Potter stars Daniel Radcliffe and Emma Watson are included by SkyBet with odds of 100/1, and comedian Russell Brand is at 33/1.
Doctor Who returns to screens on November 23 for a 50th anniversary special starring Smith and Tennant before Smith bows out in the festive episode.
Watch Matt Smith and David Tennant discuss playing The Doctor below: