Former Labour cabinet minister Peter Hain will stand down as the Neath MP at the next general election.
The former Welsh Secretary said he had "decided to draw stumps" on his Commons career following a series of discussions with the Labour leader.
Mr Hain told BBC Wales that stepping down did not mean he would be leaving politics.
Ed Miliband praised Mr Hain for his integrity, wisdom and tireless work and said he would be sorely missed.
During his lengthy career, Mr Hain served in the cabinet under the former prime ministers Tony Blair and Gordon Brown, with stints as Northern Ireland Secretary, Welsh Secretary, Work and Pensions Secretary and Leader of the House of Commons.
Mr Hain had been reselected to fight the 2015 election for Neath but said he would now find "new ways" to be involved in politics.
"Having been reselected last December as Labour candidate for Neath, I was planning to stand again next year," he said.
"However, after considerable thought and in discussion with Ed Miliband, leader of the party and for many years my close colleague, I have decided to draw stumps on my House of Commons career."
But he insisted it was not the end of his career in politics.
"It's been a difficult decision, representing Neath is fantastic, the people of Neath have been so loyal to me and I've fought hard for them and I'll continue to fight for Neath because I'm not going away," said Mr Hain.
"I'll stay active in politics, I've been in politics for over 50 years, before I was an MP and I'll remain active after I'm an MP."
Mr Hain's announcement comes just ahead of the 15th anniversary of the National Assembly for Wales which he fought for as one of the main supporters of devolution.
The MP was raised in South Africa and first came to public attention as a anti-apartheid campaigner before entering mainstream politics.
He was also a friend of the former South African president Nelson Mandela and was forced to flee South Africa in the 1960s with his parents because of their support for Mr Mandela, one of the leaders of the then banned political movement, the African National Congress (ANC).
Former Labour leader Neil Kinnock persuaded Mr Hain to join the Labour Party and he became MP for the rock-solid Labour seat of Neath in a by-election in 1991.
When Labour stormed to power in 1997 he became a whip and then a junior minister in the Welsh Office.
In October 2002, Mr Hain replaced Paul Murphy as Welsh Secretary and was then given the additional role of Leader of the Commons in June 2003.
He became Northern Ireland Secretary in May 2005, working with Mr Blair and then Irish Taoiseach Bertie Ahern to persuade all parties to end the political deadlock in the province.
In 2007 he threw his hat in the ring for the deputy Labour leadership but failed to properly register donations to his campaign, leading him to quit as Work and Pensions and Welsh Secretary the following year.
In 2009 he returned to government as Welsh Secretary.
Mr Miliband said: "A political activist and campaigner for over 50 years, Peter Hain is one of the most experienced politicians in the House of Commons in which he has served as Member for Neath for nearly a quarter of a century.
"It goes without saying that his integrity, wisdom and firmness in speaking up for those least empowered to speak for themselves, will all be sorely missed."
Neath's constituency Labour Party also paid tribute.
"For the last 23 years Peter Hain has served the people of Neath tirelessly, fighting for constituents and our Labour Party values," it said in a statement.
Tributes have also been paid by the Plaid Cymru peer Lord Dafydd Wigley of Caernarfon.
"As one who has worked with Peter Hain on devolution matters and economic issues for more than 20 years, I wish him well in his retirement from the House of Commons," he said.
"He will be remembered in Wales for his skilful leadership of the Wales Bill which led to which led to law making powers for the National Assembly for Wales.
"He will also be remembered as a great campaigner on anti racist issues and his principled support for black South Africans."