John Reid has told the BBC he will stand down as home secretary in June when "Tony Blair goes".
Mr Reid also ruled out a challenge to Gordon Brown for the Labour leadership ending months of speculation.
He told BBC One's The Politics Show he would vote for Mr Brown as leader, but would return to the backbenches rather than serve in a Brown cabinet.
The announcement means Mr Brown will not face a top level challenge for the Labour leadership.
Mr Blair is expected to announce a timetable for his departure on Thursday, but will remain as prime minister until a new Labour leader - now almost certain to be Gordon Brown - is elected.
From my point of view, it is better to take the chance, having had nine jobs in 10 years, to recharge my batteries
John Reid
Analysis: Reid resignation
Excerpts from Reid letter
Other Blairite heavyweights to have ruled themselves out in recent weeks include Environment Secretary David Miliband and Mr Reid's predecessor at the Home Office Charles Clarke.
Mr Reid told The Politics Show: "That is a natural break period because if I stay a year and leave then that will be misrepresented.
"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."
'Political courage'
In a letter to the prime minister, Mr Reid said that now the elections in Scotland, Wales and English local authorities were over and Mr Blair had indicated he was leaving, it was time to clarify his own position.
You have been an immense figure in the government over this past decade, fulfilling a number of crucial positions
Tony Blair's letter to John Reid
"I do not intend to put my name forward as a candidate in the leadership elections," he wrote.
"Whatever the pros and cons of a contest, I do not believe that there is eagerness in the party for what might be a divisive exercise at this time."
In a letter of reply, Mr Blair said he respected Mr Reid's decision but said it would be "a great loss to both country and party".
"You have been an immense figure in the government over this past decade, fulfilling a number of crucial positions at vital moments, with distinction," Mr Blair wrote.
"Your political courage, your ability to analyse and get to the heart of an issue and your understanding of people, their concerns and their hopes, has been outstanding.
"Especially at critical moments in Northern Ireland, during the essential stages of reform in the NHS and most recently in the Home Office where you gave leadership and direction in one of the most challenging jobs in government, you have a record to be proud of."
Brown 'discussion'
Mr Reid replaced Charles Clarke as home secretary last year, promising to revamp the crisis-torn department he said was not "fit for purpose".
He has said he will see through reforms to the department, which is to be split in two, before standing down.
But he has rejected the offer of a ministerial role under Gordon Brown.
Asked whether he was jumping before he was pushed, Mr Reid said: "I have discussed it with Gordon, I've had a very good discussion with Gordon on a number of these issues.
"He has made plain to me there's a place in his government for me but he understands and he accepts my decision on this.
"I have made plain to him that from the backbenches I will be there to support him, it will not be a case of sniping, it will be a case of sustaining the Labour government and the new prime minister."
He added: "In my view it is better for the Labour Party, the leadership and the new prime minister that he be given the maximum flexibility.
"In terms of introducing his new ideas, new agenda - same direction but new policies perhaps in pursuit of that, certainly new people - a fresh start bringing in younger people in many cases.
"From my point of view, it is better to take the chance, having had nine jobs in 10 years, to recharge my batteries."
Mr Brown could still face a challenge from one of two left-wing backbenchers - John McDonnell and Michael Meacher.
Mr Reid also ruled out a challenge to Gordon Brown for the Labour leadership ending months of speculation.
He told BBC One's The Politics Show he would vote for Mr Brown as leader, but would return to the backbenches rather than serve in a Brown cabinet.
The announcement means Mr Brown will not face a top level challenge for the Labour leadership.
Mr Blair is expected to announce a timetable for his departure on Thursday, but will remain as prime minister until a new Labour leader - now almost certain to be Gordon Brown - is elected.
From my point of view, it is better to take the chance, having had nine jobs in 10 years, to recharge my batteries
John Reid
Analysis: Reid resignation
Excerpts from Reid letter
Other Blairite heavyweights to have ruled themselves out in recent weeks include Environment Secretary David Miliband and Mr Reid's predecessor at the Home Office Charles Clarke.
Mr Reid told The Politics Show: "That is a natural break period because if I stay a year and leave then that will be misrepresented.
"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."
'Political courage'
In a letter to the prime minister, Mr Reid said that now the elections in Scotland, Wales and English local authorities were over and Mr Blair had indicated he was leaving, it was time to clarify his own position.
You have been an immense figure in the government over this past decade, fulfilling a number of crucial positions
Tony Blair's letter to John Reid
"I do not intend to put my name forward as a candidate in the leadership elections," he wrote.
"Whatever the pros and cons of a contest, I do not believe that there is eagerness in the party for what might be a divisive exercise at this time."
In a letter of reply, Mr Blair said he respected Mr Reid's decision but said it would be "a great loss to both country and party".
"You have been an immense figure in the government over this past decade, fulfilling a number of crucial positions at vital moments, with distinction," Mr Blair wrote.
"Your political courage, your ability to analyse and get to the heart of an issue and your understanding of people, their concerns and their hopes, has been outstanding.
"Especially at critical moments in Northern Ireland, during the essential stages of reform in the NHS and most recently in the Home Office where you gave leadership and direction in one of the most challenging jobs in government, you have a record to be proud of."
Brown 'discussion'
Mr Reid replaced Charles Clarke as home secretary last year, promising to revamp the crisis-torn department he said was not "fit for purpose".
He has said he will see through reforms to the department, which is to be split in two, before standing down.
But he has rejected the offer of a ministerial role under Gordon Brown.
Asked whether he was jumping before he was pushed, Mr Reid said: "I have discussed it with Gordon, I've had a very good discussion with Gordon on a number of these issues.
"He has made plain to me there's a place in his government for me but he understands and he accepts my decision on this.
"I have made plain to him that from the backbenches I will be there to support him, it will not be a case of sniping, it will be a case of sustaining the Labour government and the new prime minister."
He added: "In my view it is better for the Labour Party, the leadership and the new prime minister that he be given the maximum flexibility.
"In terms of introducing his new ideas, new agenda - same direction but new policies perhaps in pursuit of that, certainly new people - a fresh start bringing in younger people in many cases.
"From my point of view, it is better to take the chance, having had nine jobs in 10 years, to recharge my batteries."
Mr Brown could still face a challenge from one of two left-wing backbenchers - John McDonnell and Michael Meacher.
.