Mr Johnson faced a mixture of heckles from the opposition benches, and some Tory backbenchers, as he opened up proceedings.
But the Prime Minister enjoyed roars of support from Tory loyalists, as he addressed the House of Commons for the first time since he faced the biggest crisis of his career this week.
Sir Keir Starmer revelled in the febrile atmosphere, lapping up optimistic cheers from the Labour benches as he probed the Prime Minister on comments made by Nadine Dorries about the NHS.
Responding to questioning about the country's preparedness for the Covid pandemic and why the UK was slow in its testing plan, Mr Johnson hit back: "Nobody knew how to test for it!"
Sir Keir's questioning on NHS funding, referring back to issues faced by the Government during the pandemic, appeared to bore the House.
And Mr Johnson took his chance to rub salt into the wounds, joking: "This line of attack is not working!"
It came as Sir Keir asked: “Why did his Culture Secretary – I think she is hiding along the bench – say that successive Conservative governments left our health service wanting and inadequate when the pandemic hit?”
Boris Johnson and Sir Keir Starmer in the Commons
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Mr Johnson replied: “Everybody knows that when the pandemic hit it was an entirely novel virus for which the whole world was unprepared.
"Nobody at that stage, nobody knew how to test for it, nobody knew what the right quarantine rules should be.
“But as it happened, the UK Government and our amazing NHS not only approved the first vaccine anywhere in the world, we were the first to get it into anybody’s arms and we had the fastest rollout anywhere in Europe.”
Mr Johnson concluded his exchanges with the Labour leader, which were dominated by questions on the NHS, by insisting he wants to create high-skill, high-wage jobs.
He told the Commons: “As for jobs, I’m going to get on with mine and I hope he gets on with his.”
Opening proceedings, Mr Johnson told MPs “absolutely nothing and no one” is “going to stop us with getting on delivering for the British people”.
The Prime Minister during today's session
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Keir Starmer during PMQs
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Labour former minister Dame Angela Eagle told the Commons: “This week’s events have demonstrated just how loathed this Prime Minister is and that’s only in his own party.
“As his administration is too distracted by its internal divisions to deal with the challenges we face, can the Prime Minister explain if 148 of his own backbenchers don’t trust him why on earth should the country?”
Mr Johnson replied: “I can assure her in a long political career so far – barely begun – I’ve of course picked up political opponents all over and that is because this Government has done some very big and very remarkable things which they didn’t necessarily approve of.
“And what I want her to know is that absolutely nothing and no-one, least of all her, is going to stop us with getting on delivering for the British people.”
Mr Johnson chairing a Cabinet meeting on Tuesday
Leon Neal
It comes after a tumultuous week in Westminster that leaves the Prime Minister's, and the country's, future in doubt.
On Monday, Chairman of the 1922 Committee Sir Graham Brady confirmed that he had received enough letters to trigger a confidence vote in Mr Johnson's leadership of the Conservative Party.
A secret ballot was held on Monday evening, with the Prime Minister winning the support of 211 MPs but 148 MPs voting to oust him.
The range of issues which have caused discontent in the Tory ranks means there is no single response the Prime Minister can make to win over doubters.
While it was the Sue Gray report into lockdown parties in Downing Street which prompted the confidence vote, it also revealed deep unhappiness among MPs on different wings of the party across a range of issues.
They include promised legislation to override the Northern Ireland Protocol with the EU, as well as concerns over the high levels of tax and spending.
It comes amid reports that rebel MPs could start staging “vote strikes” on policies they oppose.
In an attempt to rebuild his standing in the party, Mr Johnson has pledged further tax cuts and is under pressure from MPs and ministers to show how he can ease the burden on households and businesses.
After Mr Johnson insisted on Tuesday it remained a “fundamental Conservative instinct” to cut taxes, Chancellor Rishi Sunak used a speech to the Onward think tank to reaffirm his intention to reduce taxes for business in the autumn.