Business leaders are calling on the next prime minister to commit to delivering HS2 in full.
In an open letter, more than 20 business leaders say continued backing for the next phase of the £56bn high-speed rail network project is vital.
Construction of the first HS2 link between London and the West Midlands is currently under way.
Business leaders want to see the line linking Birmingham, Manchester and Leeds completed as well.
The open letter, targeted at whoever wins the Conservative leadership vote out of Boris Johnson and Jeremy Hunt, has been signed by business groups including the CBI, the Institute of Directors, the Federation of Small Businesses, the British Chambers of Commerce, London First and Business Improvement Districts across the UK.
It comes almost five years after the "Northern Powerhouse" concept, first mentioned by the then Chancellor, George Osborne, in a speech on 23 June 2014.
Mr Osborne had planned to improve transport connections between the cities, towns and rural communities of the north of England and Wales, in order to increase jobs and fuel economic growth in the region.
The groups assert that the HS2 has already led to record foreign investment in the West Midlands, including the creation of 7,000 new jobs in Birmingham, with a further 100,000 more expected around the new Curzon Street and Interchange stations.
Business leaders are concerned that the forthcoming change of prime minister could lead to the rail network not being completed.
In May, a group of peers warned that HS2 would not offer value for money and risked "short-changing" the North of England.
The House of Lords Economic Affairs Committee said the project should not go ahead without a new assessment of its costs and benefits.
"We assert that committing to HS2 in full, once and for all, will spread the flow of investment across the Midlands, the North of England and into Scotland," the leaders wrote in the letter.
"The current poor connectivity in the North is a major obstacle to encouraging companies from growing in the region and is a barrier to inward investment."
According to Transport for the North, fewer than 10,000 people in northern England are able to access four or more of the region's largest economic centres within an hour.
The leaders wrote: "We urge the next prime minister and government to restate its commitment to Northern Powerhouse Rail, and its links to HS2, as a matter of urgent priority.
"We are passionate believers that this is not just a Northern issue. It is a UK issue.
"We should move away from arguments that pit Crossrail 2 in London versus Northern Powerhouse Rail; both schemes are vital for Britain's future. It's not an either/or choice. Britain needs both."
The Department for Transport told the BBC: "HS2 is well under way, with over 9,000 people and 2,000 businesses working on delivering the project right now. It will significantly improve connections between our largest cities, create extra capacity across our rail network and release capacity on some of our busiest rail lines.
"We are also clear that it is not either/or with HS2 and Northern Powerhouse Rail, as both are needed - the full benefits of NPR can only be delivered on the back of HS2."