In a pre-recorded speech to this year's Great Northern Conference, Mr Johnson said he wanted to do more than simply get through the crisis as he spoke of the nation being "still up to our thighs, in the mud of the trenches, grappling with this virus".
Repeating his pledge to "level up and unleash the talent and potential of the North", he said the job of investing in skills, education and infrastructure was "now more urgent than ever".
And he said the Government would move departments of state, Ministers, private offices and all, to great northern cities and regions that represent the future of this country".
His speech to the conference, organised by The Yorkshire Post with the Northern Powerhouse Partnership, came as millions of people across the North faced the prospect of a winter living with the tightest coronavirus restrictions.
The Government has sparked fury among northern leaders with its approach to negotiating the Tier 3 restrictions, which have so far been imposed on South Yorkshire, Greater Manchester, the Liverpool City Region and Lancashire.
Sheffield City Council leader Julie Dore called the process a "charade" and said it was clear Downing Street officials and Ministers were going through the motions for 10 days just to try and prove they were listening.
In his speech, Mr Johnson, who won an 80-seat majority in December's General Election on the back of gains made in northern England, said he would have loved for attendees at the online conference "to have got together in person for this".
He said: "Your determination not to be beaten, keep the show on the road, demonstrates the spirit with which we will defeat this resurgent virus.
"I know that many of you are putting up with restrictions, the like of which we haven't seen in our lifetime. And for those of you living under the higher alert levels in the North, you face hardships and sacrifices over and above everyone else.
"So the first thing I want to say, is a huge thank you to everyone for your heroic efforts, and particularly to local leaders who are working with us to save lives and protect the NHS, while at the same time keeping our children in school and our economy running.
"And while I do not for one moment, underestimate the challenges and difficulties that lie ahead or the heartache felt by many families, and businesses, I can tell you that this government is going to be with you every step of the way."
He added: "I have to be honest with you, this winter is not going to be easy. But I'm certain the people of Northern England will confront this crisis with the fortitude and selflessness we've seen throughout from the companies who rode to the rescue, to help to make those much needed masks and ventilators to the living angels of the North, who went further than anyone could have imagined to help each other out.
"And, of course, it must come as no surprise to any of us that Captain Sir Tom Moore, bounding around his garden with his unstoppable energy is in fact, of course, a Yorkshireman."
The Prime Minister said £3.3bn in government loans had been offered to businesses in Yorkshire, as well as more than £5bn in the North West and £3.3bn in the North East as part of the economic support package to support people's livelihoods and jobs.
South Yorkshire will receive a £41 million package of funding because of moving into Tier 3, but Sheffield City Council's leader Julie Dore pleaded with ministers to "do the right thing" and offer extra support to all Tier 3 areas.
The deal with South Yorkshire comes after bitter wrangling over money with Greater Manchester led to the highest level of restrictions being imposed from Whitehall without an agreement.
In his speech the Prime Minister said his government's 'Lifetime Skills Guarantee', which will mean that adults without an A level or equivalent qualification will be offered a free, fully-funded further education course, would provide the "the practical useful skills, we're going to need to move our economy and our country forward".
He said the Government was investing a total of £9.2bn into improving transport links as well as delivering major infrastructure projects like HS2 and the Leeds to Manchester leg of Northern Powerhouse Rail.
He said: "And alongside a £3.6bn Towns Fund to help bring a new life, a new energy, to our towns, we're bringing forward plans that will allow communities across the North to have more control over the issues that matter to them."
He concluded: "This has not been the year that any of us expected. And there's no getting away from the fact that we face the greatest crisis in this country since the Second World War.
"But I have every faith in the compassion, resilience and good sense of the British people and their determination to look out for each other in our battle against COVID.
"I want to wish everyone taking part in the Great Northern Conference every success with this year's virtual event, I heartily wish we could have got together in person and I look forward to the time when we can."