Deputy Prime Minister John Prescott is stepping down from his frontbench job after 10 years.
The Hull East MP's departure coincides with Prime Minister Tony Blair handing power to Gordon Brown after Prime Minister's Questions on Wednesday.
Unlike Mr Blair, he will remain an MP, but is hoping to take up an unpaid role on the Council of Europe, which promotes human rights and freedoms.
His job as deputy leader of the Labour Party has been taken by Harriet Harman.
She was also given the role of Labour Party chairman, previously held by her deputy leadership rival Hazel Blears.
The BBC understands it is unlikely Mr Brown will appoint a deputy prime minister to replace Mr Prescott, with his responsibilities being given to another member of the Cabinet.
When Mr Prescott announced his resignation in May, he said he was "extremely proud to have belonged to this government".
MPs said he told a private meeting on the Parliamentary Labour Party of his intentions regarding the Council of Europe on Monday.
The position of leader of the British delegation to the Parliamentary Assembly of the council is currently held by Labour MP Tony Lloyd, who is stepping down.
If he is successful, it will be Mr Prescott's second stint on the council as he served on it between 1972 and 1975.
At last year's Labour conference, Mr Prescott apologised for letting the party down, following controversies over an affair with his diary secretary, and receiving hospitality from a US tycoon.