HS2 will not offer value for money and risks "short changing" the North of England, a group of peers has warned.
A report from the House of Lords Economic Affairs Committee also said it was "far from convinced" the new high-speed railway will be built within the £55.7bn budget.
It said the project should not go ahead without a new assessment of its costs and benefits.
The government said it "fundamentally disagreed" with the report.
The committee, which includes former chancellors Lord Darling and Lord Lamont, said that more than £4bn had already been spent on the first phase of HS2, which will run between London and Birmingham.
But it said the scheme had put too much emphasis on cutting journey times and not enough on the economic impact on regions.
It said the first phase of the project offered "little benefit" to northern cities, despite them being in most need of better rail infrastructure.
And it said the second phase, which would improve journey times between Leeds and Sheffield, risked never going ahead because of spending overruns.
"The northern sections of High Speed 2 must not be sacrificed to make up for overspending on the railway's southern sections," said Lord Forsyth, who chairs the committee.
The report called for the Northern Powerhouse Rail scheme - a separate scheme connecting towns and cities in the region - to be completed alongside HS2.
Currently work on that scheme does not begin until the mid 2020s.
It also urged the government to control the costs of HS2, amid warnings that "nobody knows" what the final cost will be.
It suggested lowering the speed of HS2 or placing its terminal in west London rather than Euston would save money.
The report is the latest in a series of warnings about the railway, amid concern over its finances and environmental impact.
HS2 is planned to run up to 18 trains per hour at a top speed of 225mph, with phase one set to open in 2026.
A Department for Transport spokeswoman said: "By 2020, the government will have invested a record £13bn in transport across the North, and we have a clear plan for linking the Midlands and the North through HS2 and Northern Powerhouse Rail - the full benefits of which can only be delivered on the back of HS2.
"This is not either/or, we are clear we want both.
"HS2 will deliver additional rail capacity, significantly improve connections and provide opportunities for economic growth - with around £92bn in benefits - for people and businesses across the North."