HS2 could cost up to £22 billion more than its previous budget and be delayed by as many as seven years, the company building the railway said.
A report by HS2 Ltd chairman Allan Cook stated that the original plans "did not take sufficient account" of the effect of building a high-speed line through areas that are densely populated and with challenging ground conditions.
He added that the project's budget has "proved unrealistic", but added: "At the same time the benefits have been understated."
The Northern Powerhouse has constantly stated that both HS2 and the North's own "wish list" of transport projects must happen.
The latest news will come as a blow to hopes of levelling up what is seen as a clear North-South divide.
Mr Cook said the previous budget for HS2 was £55.7 billion but it could cost up to £78 billion, with both figures at 2015 prices.
It was due to open in phases, with the final sections from Crewe to Manchester, and Birmingham to Leeds, completed by 2033.
But the scheme is not expected to be completed until as late as 2040, Mr Cook added.
A separate review into whether to scrap the railway was launched by Prime Minister Boris Johnson last month and will be completed this autumn.
Henri Murison, Director of the Northern Powerhouse Partnership said: “The timescales for HS2 need to reflect the needs here in the North, and any delay in delivering proposed infrastructure in the Northern Powerhouse will be of concern to businesses here which support it.
"The Northern Powerhouse Partnership review into HS2 will be considering this issue and the other important questions raised in full, and they will give their judgement on how the project should proceed.
“Allan Cook’s finding of how integral HS2 is to the delivery of Northern Powerhouse Rail is clear.
"That project will also include the new line needed between Leeds and Manchester through Bradford, strongly supported by the Prime Minister in his first major domestic policy speech."
Babs Murphy, chief executive of the North and Western Lancashire Chamber of Commerce, said: "Of course, no project should have a blank cheque, but HS2 is a critical investment in the UK’s future.
"Naturally its disappointing news at the prospect of having to wait longer to see the benefits of HS2 although we remain confident the long-term benefits will be felt for generations to come and will far outweigh the initial costs.
"Our existing rail network is at capacity, with the full range of passenger and freight services sharing the same tracks and vying for priority. That’s why businesses recognise and support the strong economic case to deliver all phases of HS2.
"Many jobs have already been created in advance of its anticipated completion, and many thousands more will be created in the future. There are communities and investors basing future development plans and regeneration schemes around HS2.
"This initiative is vital to Northern Powerhouse Rail and other infrastructure projects.
"It will transform connectivity for local communities, get freight off the roads, and link up the country as a whole."
CBI Director of Infrastructure Tom Thackray said: “HS2 promises to bring huge economic benefits across the country so today’s announcement of the delay is disappointing.
"But the message from business on the project remains consistent – build it, back it, benefit from it.
“Of course today’s report may be a clarion call for those anti-HS2 voices but businesses believe derailing the scheme would be a significant economic restraint on the Midlands and The North.”
The Liberal Democrats have slammed the delay of HS2 as a 'shambles' and a 'monumental failure for the North'.
Liberal Democrat MEP for the North West Jane Brophy said: “The Tories’ long-term indecision and incompetence was always going to cost taxpayers and fail Northerners the most.
“The Liberal Democrats have always been absolutely clear that HS2 construction should have started in the North. Then, when the project inevitably encountered the issues it has, the areas most in need of infrastructure upgrades would have received them first.
“However, as things stand, rail links in London and the South will still be upgraded, whilst Northern links are left in their dire 1970s state – as usual."