The presenter and novelist has co-hosted the BBC quiz show with university friend Alexander Armstrong since its debut in 2009.
After filming more than 1,300 episodes and nearly 30 series, he will be leaving the show but will continue to appear on the celebrity specials.
Richard said in a statement: “Pointless has been a joy from start to finish, working alongside my friend Alexander Armstrong, backed by the most wonderful team, and for the best viewers in the world.
“I will miss everyone so much, but I’m thrilled that I’ll still be presenting the celebrity shows. I can’t thank everyone enough for twelve amazing years.”
In recent years, Richard has explored different avenues away from Pointless, releasing his debut novel, The Thursday Murder Club, in September 2020, which became a bestseller.
It is set to be turned into a film after the right’s were purchased by Steven Spielberg’s production company Amblin Entertainment.
Richard also fronts his own gameshow for BBC Two, Richard Osman’s House of Games.
Having started out in TV as a producer, Richard worked on Deal Or No Deal before appearing on the other side of the camera in Pointless.
He was not originally intended to be Alexander’s co-presenter, but after filling the role as part of a demonstration laid on for the BBC, executives asked him to continue for the first series, and he has been there ever since.