Boris Johnson is self-isolating after meeting an MP who later tested positive for Covid-19.
The prime minister said he was contacted by NHS Test and Trace on Sunday but is not showing symptoms.
Mr Johnson on Thursday spent about 35 minutes with Ashfield MP Lee Anderson who has since tested positive.
The news came as No 10 said Mr Johnson would make "critical announcements" about coronavirus and "levelling up" the UK over the coming weeks.
In an announcement planned before Mr Johnson was told to self-isolate, Downing Street said there would be a "clear signal" of his "ongoing ambitions for the United Kingdom".
It said Mr Johnson would chair "key Covid meetings" and work with Chancellor Rishi Sunak to devise the upcoming spending review with an aim to fulfil his promise to "build back better".
But No 10's effort to start the week afresh following the departure of two of Mr Johnson's top aides amid an internal power struggle was overshadowed by news the prime minister was self-isolating.
Mr Johnson wrote on Twitter on Sunday night: "Today I was notified by NHS Test and Trace that I must self-isolate as I have been in contact with someone who tested positive for COVID-19.
"I have no symptoms, but am following the rules and will be working from No 10 as I continue to lead the government's pandemic response."
A No 10 spokesman added: "The PM is well and does not have any symptoms of Covid-19."
'I've been pinged!'
In a WhatsApp message to Tory MPs seen by the BBC the PM added: "The good news is that NHS Test and Trace continues to improve. The bad news is that I have been pinged!"
He said that he would observe self-isolation rules despite "following the guidance and socially distancing" during his meeting with Mr Anderson.
"It doesn't matter that I feel fine - better than ever - or that my body is bursting with antibodies because I have already had the damn thing," he added.
"The rules are the rules and they are there to stop the spread of the disease."
In April, Mr Johnson spent three nights in intensive care after falling ill with the virus.
He later said it "could have gone either way" and thanked healthcare workers for saving his life.
'Timing couldn't be worse'
Boris Johnson will now have to stay at home in No 10.
It means he will not be able to be in Parliament, though I'm told he will be working from Downing Street.
He does still intend to keep communicating with the country.
It was supposed to be a pretty big week for Boris Johnson - he is trying to reset his government after some factional fighting in his office over the last few days.
There are conversations taking place with the parliamentary authorities to see whether he can still contribute to the Commons.
I think it is fair to say this has not come at the best time for Mr Johnson: he has big decisions to make on Brexit and what happens when England's lockdown ends on 2 December.
And it is also worth bearing in mind he was extremely ill with coronavirus earlier in the year and we do not know what getting the virus does for a person's immunity.
Leader of the House of Commons Jacob Rees-Mogg said on Sunday evening he was urgently exploring how to "support additional virtual participation" in the chamber following a campaign by vulnerable MPs.
Such a move could allow more MPs, including Mr Johnson, to attend Commons' debates virtually and possibly even Prime Minister's Questions as he self-isolates.
On Thursday, Conservative MP Mr Anderson posted a photo of himself with Mr Johnson at No 10 alongside the words: "Breakfast with the PM."
Mr Anderson posted on his Facebook page to say he was self-isolating with his wife, who is clinically vulnerable.
"On Friday I lost my sense of taste at the same time my wife had a bad headache," he said. "I had no cough, no fever and felt well. We both had a test on Saturday and the result came in Sunday morning.
"My wife and I both tested positive. I feel absolutely fine and my biggest concern is my wife who is in the shielded group.
"But we are both feeling good."
BBC political editor Laura Kuenssberg tweeted the news had come the night before what was meant to be a "big relaunch week", following the row last week involving the PM's chief adviser Dominic Cummings.
Mr Cummings left Downing Street for the last time on Friday following internal battles about his role.
Earlier this weekend, senior Tory MP David Davis said Mr Cummings' departure was a chance to "reset government".
Another Conservative MP, Sir Charles Walker, said the changes were a sign of Mr Johnson's "determination to rebuild relationships".
A meeting between the PM and the Northern Research Group of backbench Tory MPs had been scheduled for Monday.
Officials also confirmed the government's 10-point plan for a "green industrial revolution" would be published "to boost green jobs whilst invigorating plans to achieve net zero by 2050".
In addition, another week of negotiations over a post-Brexit trade deal with the EU are set to begin in Brussels.
The transition period, which followed Brexit in January, ends on 31 December by which time a deal needs to be agreed and approved by parliaments in the UK and EU.
Chief UK negotiator David Frost has said there had been some progress between the two sides but that considerable differences remained.
The UK government announced another 24,962 confirmed Covid cases on Sunday, as well as a further 168 deaths within 28 days of a positive test.