After four years as the Time Lord on Doctor Who, viewers will see Matt Smith’s Doctor regenerate in the 2013 Christmas special.
Matt Smith, 30, said working on the show had been “the most brilliant experience”.
Doctor Who marks its 50th anniversary in November with a special episode, which Matt Smith has already filmed.
Matt Smith’s “spectacular exit” was yet to be revealed and would be “kept tightly under wraps”.
He first stepped into the Tardis as the 11th Doctor in 2010. Taking over from David Tennant, he was the youngest actor to play the role of the Doctor.
Speaking after the announcement, Matt Smith said he was “incredibly proud” of what the show had achieved over the last four years under Steven Moffat, the show’s lead writer and executive producer.
Matt Smith also thanked fans around the world for their “truly remarkable” dedication to the show.
During his tenure, Matt Smith’s floppy-haired, bow tie-wearing Time Lord has fought enemies such as the Daleks, Cybermen, Weeping Angels and the Silence.
His Doctor has shared his adventures with Amy Pond (Karen Gillan), Rory Williams (Arthur Darvill) and most recently, Clara Oswald (Jenna-Louise Coleman).
Referring to his time-travelling companions, Matt Smith said: “It’s been an honor to play this part, to follow the legacy of brilliant actors, and helm the Tardis for a spell with ‘the ginger, the nose and the impossible one’. But when ya gotta go, ya gotta go…”
Show runner Steven Moffat said: “Every day, on every episode, in every set of rushes, Matt Smith surprised me. The way he’d turn a line, or spin on his heels, or make something funny, or out of nowhere make me cry – I just never knew what was coming next.
“The Doctor can be clown and hero – often at the same time – and Matt rose to both challenges magnificently. And even better than that, given the pressures of this extraordinary show, he is one of the nicest and hardest-working people I have ever had the privilege of knowing. Whatever we threw at him – sometimes literally – his behavior was always worthy of the Doctor.”
Steven Moffat added: “Great actors always know when it’s time for the curtain call, so this Christmas prepare for your hearts to break as we say goodbye to number 11. Thank you Matt – bow ties were never cooler.”
The announcement of Matt Smith’s exit is likely to spark months of fevered speculation about his replacement.
“Somewhere out there right now – all unknowing, just going about their business – is someone who’s about to become the Doctor,” Steven Moffat hinted.
“A life is going to change, and Doctor Who will be born all over again. After 50 years, that’s still so exciting.”
Matt Smith’s first adventure in April 2010, the Eleventh Hour, saw his newly-regenerated Doctor crash his Tardis into the garden of a young Scottish girl who was later to become his new companion – Amy Pond.
In his most recent adventure, the Name of the Doctor – which aired two weeks ago – Matt Smith’s Time Lord visited his own grave on the planet Trenzalore.
In 2011, Matt Smith became the first actor to be nominated for a BAFTA in the role.
And he won the most popular male drama performance award at the National Television Awards in 2012.
Born in Northampton in 1982, Matt Smith studied drama and creative writing at the University of East Anglia.
He made his TV debut in the 2006 adaptation of Philip Pullman’s the Ruby in the Smoke, which starred former Doctor Who companion Billie Piper.
Matt Smith’s stage work has included stints with theatre companies such as the Royal Court and National Theatre. His West End debut was in Swimming With Sharks opposite Christian Slater.
During his time in Doctor Who, Matt Smith also appeared in TV films Christopher and His Kind, in which he played novelist Christopher Isherwood, and in Olympic rowing drama Bert and Dickie.
Doctor Who: The 11 Doctors
1. William Hartnell (1963-1966)
2. Patrick Troughton (1966-1969)
3. Jon Pertwee (1970-1974)
4. Tom Baker (1974-1981)
5. Peter Davison – pictured (1982-1984)
6. Colin Baker (1984-1986)
7. Sylvester McCoy (1987-1996)
8. Paul McGann (1996)
9. Christopher Eccleston (2005)
10. David Tennant (2005-2010)
11. Matt Smith (2010 – 2013)
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