Senior management at the newspaper are "actively considering" moving back to the Guardian’s birthplace in Manchester, according to The Times.
The move could happen within two years, The Times reported, with editor Kath Viner said to be in favour of the move that would involve most editorial and administrative staff.
The Media Village in Salford, which is now home to thousands of staff from the BBC and ITV, would be an obvious location for the move.
Karen Bradley, the culture secretary, proposed last month that Channel 4 should also leave the capital.
Guardian Media Group, the publisher of the Guardian and the Observer, is in the middle of a plan to turn around years of heavy losses by cutting costs by 20%.
Last month the papers’ 1,500 staff were warned of compulsory redundancies as the business seeks to break even by the 2018/19 financial year.
The Guardian is also considering shrinking the paper size to tabloid and outsourcing printing to rival News UK, it was reported in January.
The Manchester Guardian was launched in 1821 and the newspaper began moving staff to London in the 1960s. It moved from London's Farringdon to King's Cross in 2008.
A Guardian News & Media statement said: "We are always looking at ways to reduce our cost base, including where different functions are located, but we have no plans to leave Kings Place at present."