Andy Burnham has urged Theresa May to guarantee that plans for the Northern Powerhouse remain alive after her committee on the economy and industrial strategy met for the first time.
The shadow home secretary raised concerns that focus could be shifting away from reviving the fortunes of the northern cities to a broader redistribution of the economy away from London and the South East.
Mr Burnham warned scrapping the Northern Powerhouse scheme, a brainchild of former chancellor George Osborne, would be "the biggest betrayal of people in the North of England since Margaret Thatcher tore the heart out of many of its industrial communities in the 1980s".
After entering No 10 Mrs May appointed Andrew Percy, the MP for Brigg and Goole, as Northern Powerhouse minister and the plans were described as a "key government priority" by the Government.
At the inaugural meeting of the new Cabinet committee on Tuesday, Mrs May stressed the Government should focus on delivering "an economy that works for all".
However Mr Burnham, MP for Leigh in Greater Manchester, suggested the PM appeared to have "changed her tune" from earlier pledges to close the so-called North-South divide.
He said: "The new Prime Minister and her entire Cabinet were elected just over 12 months ago on a manifesto promise to build a Northern Powerhouse.
"If Theresa May is now ripping that up, it will be the biggest betrayal of people in the North of England since Margaret Thatcher tore the heart out of many of its industrial communities in the 1980s.
"As the recent EU Referendum result showed, those communities feel abandoned by Westminster. The right response, surely, is to improve the promises that have been made to them, not abandon them."
Mr Burnham said such a change in policy would increase a "crisis of confidence in our democracy" as the Northern Powerhouse would end up as "nothing more than meaningless spin".
He added that the possibility the plans were in jeopardy reinforced his candidacy to be elected mayor of Greater Manchester in May next year.