He will bow out in the Christmas special when he will be replaced by a new incarnation of the Time Lord.
Smith, 30, who has been in the role since 2010, said it had been "an honour" to play the part.
He said: "Doctor Who has been the most brilliant experience for me as an actor and a bloke, and that largely is down to the cast, crew and fans of the show.
"I'm incredibly grateful to all the cast and crew who work tirelessly every day, to realise all the elements of the show and deliver Doctor Who to the audience.
"Many of them have become good friends and I'm incredibly proud of what we have achieved over the last four years."
Smith, who recently made his directorial debut with Cargesee for Sky Arts, has spoken about ambitions for a film-making career.
He became the eleventh, and youngest, incarnation of the Time Lord when he was unveiled as the new Doctor.
He replaced David Tennant who had taken over from Christopher Eccleston in 2005.
It is not yet known who will replace Smith as the Doctor. His most recent on-screen companion, played by Jenna-Louise Coleman, will stay with the show.
Doctor Who marks its 50th anniversary in November with a special episode, which Smith has already filmed.
Smith's departure has sparked speculation over who would be his replacement. Favourites include Damian Lewis, the Homeland star, or that Tennant may make a return.
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For Doctor Who Fans: Who would you like to see replace him?