Sajid Javid has said he wants to see a return to normal "as quickly as possible" after replacing Matt Hancock as health secretary.
Speaking on Sunday, Mr Javid said he would do all he could to "deliver for the people of this great country".
His appointment comes after Mr Hancock stood down on Saturday for breaching Covid rules by kissing a colleague.
Mr Javid, who has had several key government roles, said his predecessor had worked "incredibly hard".
His return to the cabinet comes 16 months after his shock resignation as chancellor.
But Labour criticised the appointment, saying he had been an "architect of austerity" that weakened the NHS.
Mr Hancock announced his resignation after pressure had been building for him to quit following the publication by the Sun of pictures and a video of him and Gina Coladangelo, who are both married with three children, kissing.
The newspaper said the images had been taken inside the Department of Health and Social Care (DHSC) on 6 May.
Following the revelations, a number of Conservative MPs, as well as Labour and the Covid-19 Bereaved Families for Justice group, had called for Mr Hancock to go.
Ms Coladangelo is also leaving her role as a non-executive director at the DHSC.
Mr Hancock has ended his 15-year marriage to his wife, Martha, and the relationship with Ms Coladangelo is understood to be a serious one.
Mr Javid's return to a senior cabinet role comes after he abruptly left government in February last year, a month before he was due to deliver his first Budget.
At the time, the prime minister ordered him to fire his closest aides and replace them with advisers chosen by Number 10 if he wanted to remain in post - conditions he said he was "unable to accept".
Mr Javid, who had clashed with the prime minister's former chief adviser, Dominic Cummings, chose to quit instead and was replaced by his former deputy at the Treasury, Rishi Sunak.
Speaking on Sunday to reporters, Mr Javid said Mr Hancock had achieved "a lot" in the role, adding "I'm sure he will have more to offer in public life".
He said: "I was honoured to take up this position. I also know that it comes with huge responsibility, and I will do everything I can to make sure that I deliver for the people of this great country.
"We are still in a pandemic and I want to see that come to an end as soon as possible, and that will be my most immediate priority to see that we can return to normal as soon and as quickly as possible."
On Sunday the UK reported a further 11 deaths within 28 days of a positive coronavirus test and a further 14,876 cases of Covid-19. Due to a technical issue the data from England was incomplete with any outstanding cases to be reported on Monday.
It is, of course, stating the obvious to say Sajid Javid has a full in-tray as the new health secretary in England.
While we may be over the worst of the pandemic, there is still some way to go before life returns to normal.
For one thing hospital admissions for Covid are rising - not enough to overwhelm the NHS but enough to disrupt the recovery of other services like cancer care and routine surgery.
The NHS in England is also in the process of recruiting a new chief executive, while the UK Health Security Agency is being set up and absorbing some of the work of key agencies involved in the pandemic response, such as NHS Test and Trace and Public Health England.
Then there is the long-term reform of the NHS that was announced earlier this year, which is overhauling some of the management structures of the health service by creating integrated organisations bringing together hospital and community teams.
If that was not enough, there is growing pressure on the government to finally come up with plans for the funding of social care - something governments of all colours have been promising to do since the turn of the century.
In a video on Twitter explaining why he had resigned, Mr Hancock said he understood the "enormous sacrifices that everybody in this country has made, that you have made, and those of us who make these rules have got to stick by them and that's why I have got to resign".
In his resignation letter, he apologised to his family and loved ones for "putting them through this".
In response, the prime minister said Mr Hancock "should leave office very proud of what you have achieved - not just in tackling the pandemic, but even before Covid-19 struck us".
But Labour's shadow health secretary, Jonathan Ashworth, said the prime minister should have sacked Mr Hancock on Friday, when the revelations first emerged.
"Boris Johnson should have had the guts, the spine, the awareness, the judgement to sack [Matt Hancock] on Friday," he told BBC Breakfast on Sunday.
Mr Ashworth added that Mr Hancock's record on care homes, PPE, test and trace and sick pay for those isolating during the pandemic was "a damning legacy".
He also criticised Mr Javid's appointment, saying "given his record on austerity, it's a bit like putting the fox in charge of the chicken coop".
Dr Chaand Nagpaul, chairman of the British Medical Association Union, said Mr Javid would face a "baptism of fire" in his new role without the normal phased handover other health secretaries enjoyed.
The healthcare workforce was "absolutely exhausted" after working through the pandemic and there was a "backlog crisis" of more than five million patients waiting for treatment, he said.
But the first priority for Mr Javid will be overseeing the vaccination programme, Mr Nagpaul said, adding: "He needs to make sure that every day counts because until we've vaccinated the adult population we are not going to be able to see our way through this pandemic."
Honoured to have been asked to serve as Secretary of State for Health and Social Care at this critical time.— Sajid Javid (@sajidjavid) June 26, 2021
I look forward to contributing to our fight against the pandemic, and serving my country from the Cabinet once again.
Before serving as chancellor, Mr Javid was home secretary.
He has also led the housing, communities, business and culture departments.
One of his first jobs as health secretary will be to examine the data ahead of England's proposed end to Covid restrictions on 19 July.
Former health secretary Jeremy Hunt described his appointment as an "excellent choice", saying it was the best possible news for social care because his time at the Department for Communities and Local Government meant he "gets it".