Former Cabinet minister Clare Short says she will be stepping down as a Labour MP at the next General Election.
Ms Short led backbench criticism of the most recent war in Iraq
Ladywood MP Ms Short, 60, partly blamed Tony Blair's foreign policy and said: "I have reached a stage where I am profoundly ashamed of the government."
She told the BBC she wanted to campaign for electoral reform. She did not rule out standing to be an independent MP.
The government chief whip says Ms Short is likely to face disciplinary action over her comments.
Chief Whip Jacqui Smith said in a statement: "Clare Short's public admission that she would welcome the defeat of her Labour parliamentary colleagues and the Labour government at the next general election are completely unacceptable.
"I have previously made this clear to her.
"As chief whip, I can recommend the whip be withdrawn from parliamentary colleagues or suspend them from the whip.
"However, Clare Short's comments and actions are so serious, I am now taking the matter further by referring her conduct to the party chair and the general secretary of the Labour Party."
A Labour Party source said it would be difficult to remove the Labour whip from Ms Short quickly because it needed a vote from Labour MPs, who were still on their summer break.
"We are fast-tracking it," the source told the Press Association.
"The whips and backbench MPs are so incensed by this that it's gone straight to the top."
The most serious penalty that could be imposed is expulsion from the party.
Ms Short quit as international development secretary in 2003 in protest at the post-invasion plans for Iraq and is now set to stop being a Labour MP.
She told the BBC the option of standing as an independent was "improbable, but who knows?".
Ms Short made her announcement in the Independent, in which she wrote: "Blair's craven support for the extremism of US neoconservative foreign policy has exacerbated the danger of terrorism and the instability and suffering of the Middle East.
"He has dishonoured the UK, undermined the UN and international law and helped to make the world a more dangerous place."
She also pointed to the replacement of Trident, public sector reform and Mr Blair's style of government as other reasons.
Ms Short has resigned from the Labour Party front bench three times - twice over the Gulf Wars and once because of the prevention of terrorism laws.
The way she resigned from the Cabinet in 2003 was seen as damaging her standing with the Labour left.
Rather than quitting before the conflict, like Cabinet colleague Robin Cook, she publicly agonised over its rights and wrongs.
She only left her post as international development secretary once the main hostilities ended.
She was one of a number of MPs who demanded Parliament be recalled last month to discuss the crisis in the Middle East.
Ms Short said another reason she wanted to quit as a Labour MP was because she wanted to campaign for a hung Parliament and to encourage electoral reform.
She said Labour should hold a third of the seats, the Tories a third and the rest should be made up of Greens and other parties.
With a degree in political science, she had no notion of entering Parliament until she worked as a private secretary to Conservative Home Office Minister Mark Carlisle, and found many MPs decidedly "unimpressive" at their jobs.
"I could do that," she thought, and in 1983, she became the member for Birmingham Ladywood.
In more recent times she stunned Westminster by introducing her secret son, Toby, to the public, 31 years after she had given him up for adoption.
Earlier this year, Jon Norton, husband of the late former Northern Ireland Secretary Mo Mowlam, announced that he was having a relationship with Ms Short.