John Reid's decision to quit as home secretary "is a sign of the change to come" when Tony Blair leaves Number 10, says Labour chairwoman Hazel Blears.
Ms Blears, who hopes to become Labour's deputy leader, welcomed the prospect of a "huge amount of change" bringing new "dynamism" and a "renewal of ideas".
Mr Reid was the last heavyweight to rule out challenge for the leadership.
Gordon Brown is now seen as a near certainty to succeed Mr Blair as prime minister when he steps down next month.
Mr Blair is expected to resign as Labour leader on Thursday this week, but will stay as prime minister while the seven week process of choosing his successor takes place.
Despite speculation over recent months that there might be a challenge to Mr Brown from a Blairite minister, all those seen as credible candidates have ruled themselves out.
Mr Reid, who has never been seen as close to Mr Brown, has also decided to step down from his job at the same time as Mr Brown becomes prime minister.
Asked about that move, Ms Blears told Sky News: "I think this is a sign of the change to come.
"John Reid has been a fantastic minister for the last 10 years. He's done a whole range of jobs, he's made differences to our life in this country.
"But I think that his decision to stand down means we will get a huge amount of change."
However ex home secretary David Blunkett said the timing of Mr Reid's departure was "not terribly good" given that he had not been in the post very long and was in the process of splitting the Home Office.
Mr Blunkett told the BBC he had spoken to Mr Reid and believed him when he said he would not be "sniping" from the backbenches.
But he said the timing of Mr Reid's departure, in the midst of the departmental "deconstruction and reconstruction", meant "there must be very profound reasons that have driven him to do so".
Despite the lack of any apparent heavyweight challenge Mr Brown could still face a challenge from one of two left-wing backbenchers - John McDonnell and Michael Meacher.
But they are given little realistic chance of beating him and speculation around Westminster has now shifted on from whether Mr Brown will succeed Mr Blair, to who will be in his Cabinet team.
Newspaper speculation suggests Jack Straw may replace Mr Reid as home secretary in what would mark a big turnaround in fortunes for the man demoted from foreign secretary to Commons leader last year.
Mr Straw's experience as home secretary from 1997-2001 mean he is seen as someone who could hit the ground running the post, the reports say.
There has been growing speculation as well about who will replace Mr Brown as chancellor when he moves to Number 10. Mr Straw, David Miliband and Alistair Darling have all been linked with the job at times.
The futures of all "Blairite" ministers are in the spotlight after years in which there have been times of tensions between the backers of Mr Blair and Mr Brown.
Mr Reid sought to play down the prospect that he was quitting to lead opposition to Mr Brown, telling told BBC One's The Politics Show it was a "natural break period".
"Now I've done nine jobs in 10 years and I think from my point of view I think it's a good thing to be able to go out to listen, to learn, to discuss, to get back to the grass roots.
"But also from the point of view of an incoming prime minister. I think the new prime minister should have the maximum flexibility. He needs space."
Northern Ireland Secretary and deputy leadership contender Peter Hain told the BBC's Westminster Hour relations had always been strained between Mr Reid and Mr Brown.
"There's no getting away from the fact that he and Gordon have never been political bosom buddies, but I don't think that's at the bottom of his decision," he said.