He is taking over as the chairman of the Scott Trust which owns Guardian Media Group.
Mr Rusbridger, who joined the newspaper as a reporter in 1979 and became the editor in 1995 after succeeding Peter Preston, told staff his time in charge had “been quite an extraordinary period in the life of The Guardian”.
He said: “In February 1995 newspaper websites were, if they existed at all, exotic things: we were still four years off launching Guardian Unlimited.
“Since 1999 we’ve grown to overtake all others to become the most-read serious English language digital newspaper in the world.”
In his time as the editor, he has guided the newspaper through a major change in format.
It went from a broadsheet to a Berliner style when many of its rivals went tabloid - and a move of its offices from London’s Farringdon to King’s Cross.
He has steered The Guardian through the online revolution which has seen it commit itself to the principle of open access and attempt to become an international brand with offices in Australia and the United States.
Dame Liz Forgan, whom he will replace at the trust, said he had been the paper’s “driving force ... for a generation”.
The newspaper - along with the Washington Post - won the Pulitzer Prize for journalism this year for its work on secret surveillance work carried out by the American National Security Agency.
Mr Rusbridger’s career began at the Cambridge Evening News and he has also worked at The Observer and the London Daily News. He is the author of three children’s books and co-wrote a BBC One drama about a conspiracy involving GM crops called Fields of Gold.
Mr Rusbridger married Lindsay Mackie in 1982, and the couple have two daughters. One of them, Bella Mackie also writes for The Guardian using her mother’s maiden name.
The trust will appoint the new editor, although newsroom staff are traditionally balloted on who they want to see take the role.