The emphasis on the domestic agenda continued to fuel speculation the PM is keeping his options open for a snap general election, despite his strong denials.
The PM said: “We are going now to have a £3.6 billion Towns’ Fund supporting an initial 100 towns, so that they will get the improved transport and the improved broadband connectivity that they need.”
The PM gave his backing to the trans-Pennine transport link between Manchester and Leeds which is intended to help “turbo charge” regional growth.
Mr Johnson 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.”
In a clear pitch to traditional Labour voters, Mr Johnson insisted that politicians had failed people in the North.
He said: “The centre of Manchester, like the centre of London, is a wonder of the world.
“A few miles away from here, the story is very different.
“The story has been for young people growing up there of hopelessness, or the hope that one day they will get out and never come back.
“The crucial point is it certainly isn’t really the fault of the places, and certainly isn’t the fault of the people growing up there.
“They haven’t failed. It’s we, us, the politicians, our politics has failed them.”
Mr Johnson set out the four “ingredients” for the success of the UK as livability, connectivity, culture, and power and responsibility.
He said this means areas having great public services, enough affordable homes, safe streets, fast broadband, and more responsibility and accountability for local areas.
Mr Johnson insisted the country had to “get ready” for the prospect of a no-deal Brexit.
He said: “On the… risk of a no-deal Brexit, or the prospect of a no-deal Brexit, well, we have just got to get ready for it.
“I don’t think that’s where we will end up.
“But as I have told our European friends, we are going to prepare very actively for that eventuality in high confidence that this is an amazing country and we will get through it if we need to.”
Mr Johnson said he had “very friendly relations” with other EU leaders.
He added: “As to whether my friends across the Channel are warming to me, well I have always had very good relations.
“I have very friendly relations with the other EU foreign ministers already and EU leaders as well.
“We will build on them.”
Downing Street said that detailed plans regarding the proposed Manchester to Leeds rail route will be published in the autumn, following a review into HS2.
The trans-Pennine route is expected to cut journey times and provide additional capacity for people across the region.
Mr Johnson used the speech to state he is committed to “rebalance power, growth and productivity across the UK”.
The PM 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”.
Leader of the opposition Jeremy Corbyn compared Mr Johnson's speech to former Chancellor George Osborne's proposal to deliver HS3 to a "northern global powerhouse" - back in 2014.
Mr Corbyn said: "All he's done is gone to Manchester to the exact same place as George Osborne did five years ago and announce the same thing and it still hasn't happened.
"What the north really needs is a Crossrail for the north which would be a proper connectivity with Newcastle and with Hull."
Shadow transport minister Rachael Maskell said: "It's quite embarrassing the Prime Minister had to ask people to applaud his announcement of a faster line between Leeds and Manchester.
"It's quite clear the northern audience know that it's not even a half measure and not worth clapping.
"This is sadly once again another Tory Prime Minister coming to the north with nothing new.
"There is no timeline, no linking of northern towns, just more vague promise of a skeleton line, and a rehash of the insulting level of investment for the region that Theresa May tried and failed to bribe Labour MPs with a few months ago.
"Instead of backing Labour's Crossrail for the North, Johnson is offering a cheapskate refurb of existing lines. There is no timeline on delivery.
"Boris Johnson failed to answer key questions today such as whether he'll reverse the decision not to electrify the trans-Pennine rail line and whether it will be upgraded for freight."
National Infrastructure Commission chairman Sir John Armitt said: "The PM's decision today must be integrated with plans for HS2, and matched with devolved funding and powers for city leaders in the north."