Johnson promises new high-speed rail line between Leeds and Manchester
The new prime minister says he wants to do with "Northern Powerhouse Rail what we did with Crossrail in London".
Pledging new intercity rail routes across the north, with Manchester to Leeds as the first step, the prime minister said: "I want to be the PM who does with Northern Powerhouse Rail what we did with Crossrail in London.
"And today I am going to deliver on my commitment to that vision with a pledge to fund the Leeds to Manchester route.
"It will be up to local people and us to come to an agreement on the exact proposal they want, but I have tasked officials to accelerate their work on these plans so that we are ready to do a deal in the autumn."
Downing Street said detailed plans would be published in the autumn following a review of the HS2 - the high-speed line that will link London, the Midlands and the north.
"This is a seminal moment for the north," said Northern Powerhouse Partnership director Henri Murison.
"It is heartening to see the first major policy announcement by the new prime minister is to benefit the north - matching the commitment of businesses already investing here."
Building on his commitments when he entered Downing Street, the prime minister also used his speech in Manchester to set out his vision to rebalance power, growth and productivity across the UK, and said his focus would not just be on major infrastructure projects.
He pledged to "improve the unglamorous local services which people use every day," such as buses, saying it is about "services within cities, not just services between cities".
The PM said - starting with plans for Manchester - he wanted more exclusive bus corridors, higher frequency services and low and zero emissions buses.
Mr Johnson also spoke about other pledges to boost education and social care, as well as a £3.6bn fund to help 100 towns improve things such as transport and broadband.
"And I want that to start now, with improvements that can happen in the short term, not just big engineering schemes that will take years."
Mr Johnson defended his plans and denied he would struggle to find the many billions needed for the rail project and other major pledges announced this week, such as 20,000 more police.
"The plans we're announcing I think have been pretty reasonable. Everyone knows there is fiscal headroom for the education spending... the police spending is widely applauded and supported. And yes, we want to go ahead with Northern Powerhouse Rail.
"I think the return on investment for this country would be colossal."