David Miliband is to quit UK politics for a role with a leading aid charity in New York in what has been described as a "big loss" for Labour by MPs.
The former foreign secretary will end speculation of a frontline comeback in his brother Ed's shadow cabinet by stepping down as an MP, the Daily Mirror reported.
The leading Blairite, unexpectedly beaten to the party leadership by his younger sibling in 2010, will head to the US to work for the International Rescue Committee, it said.
The move will spark a by-election in the usually safe Labour South Shields seat, which Mr Miliband has held since 2001 and in which he secured a 11,109 majority in 2010, polling 52% of the vote.
The news took Westminster by surprise after recent speeches had fuelled speculation he would finally take up the "open door" his brother had consistently proffered. MPs took to Twitter to bemoan the departure of such a prominent figure - once considered the overwhelming favourite to follow Gordon Brown as leader. Keith Vaz was among those to describe it as a "huge loss to British politics" and the party. "The best and the brightest leaving the country," he added.
Ex-cabinet minister Lord Mandelson insisted however that it did not mean a final curtain on the once-glittering political career of Tony Blair's long-time policy chief. "He just combined policy, good judgment, real concern, a knowledge of economics and an ability to tie things together," he told BBC Radio 4's The World Tonight.
Shadow energy secretary Caroline Flint said she was happy for her former cabinet colleague and his family - and made a joke about his new job. Mr Miliband was nicknamed "Brains" by former Number 10 spin chief Alastair Campbell after the character who worked for International Rescue in the 1960s Thunderbirds TV show. "Here's to International Rescue - Thunderbirds are go!", Ms Flint wrote.
Mr Miliband quit the shadow cabinet after losing the knife-edge vote for the party leadership to his younger brother, saying he did not want to be a "distraction". They have both admitted that it was a bruising encounter - in which David was clear favourite and lost out because Ed secured trade union votes - that strained family ties.
He has remained on the backbenches but fuelled talk of a frontline comeback earlier this year with a vocal Commons attack on the Government's benefit changes. As recently as November, he said he intended to remain an MP.
Liberal Democrat president Tim Farron said: "It's a big loss for parliament. David was a big thinker, great politician and a lovely man," while Conservative Party chairman Grant Shapps said: "This is a surprising decision from David Miliband. He has contributed a great deal to British politics and we wish him well."