Borough MP Andy Burnham will step down from the House of Commons after 16 years as representative for Leigh even if he loses out in the mayoral elections.
The shadow home secretary first indicated plans to leave his post at the Labour Party conference in September 2016 but said the decision for a snap General Election had brought his plans forward.
He said: “We are living through a crisis in politics and the Westminster system is in my view a major part of the problem.
“We could hold as many General Elections as we like and yet Westminster would still be structurally incapable of developing a real response to the deep-rooted issues revealed by last year’s referendum. Real change is needed rather just a change of faces.”
Burnham said he believed a “devolution” of power, passing power from the central government to local authorities, would be the “best chance we will ever get to secure a more equal country.”
He said: “That is why I have decided to devote myself to it.”
Burnham will go head-to-head for the position of Mayor of Greater Manchester with Conservative candidate Sean Anstee in May.
Burnham lost to current Labour leader Jeremy Corbyn in the 2015 leadership election before accepting the role of shadow home secretary.
In his former role as health secretary in 2010, Burnham had proposed a 10% ‘death tax’ on mid to high earners, which was later branded “totally unfair” by some.