Officers were looking into "potential breaches of Covid-19 regulations" in Downing Street and Whitehall since 2020, Commissioner Cressida Dick said.
She added that the investigation was launched after an internal inquiry led by civil servant Sue Gray passed information to the force.
His spokesman said the PM did not believe he had broken the law.
BBC political editor Laura Kuenssberg said Ms Gray's report is essentially complete, and it was likely to be published on Wednesday.
But she added No 10 would not see the report on Tuesday evening, meaning it was not expected to be published before Prime Minister's Questions.
For months, the prime minister has been dogged by reports of staff parties in Downing Street, some attended by him, when lockdown laws preventing social mixing were in force.
The PM has apologised for attending a "bring your own booze" event on 20 May 2020, during the first lockdown, saying he thought it was a "work event".
Dame Cressida would not say which parties were being investigated by the force, and while breaches of regulations can result in fixed penalty notices, the police inquiry did not mean they would be issued "in every instance and to every person involved".
Labour deputy leader Angela Rayner renewed calls for Mr Johnson to resign in light of the inquiry, calling him a "national distraction".
In the Commons, she said "potential criminality has been found in Downing Street", and that the need for a police investigation into No 10 parties was "a truly damning reflection on our nation's very highest office".
Boris Johnson told the Commons he welcomed the investigation, as it would "give the public the clarity it needs" over the allegations.
And Paymaster General Michael Ellis called for MPs to "let the investigation run its course and not pre-empt its conclusions".
Mr Johnson - who was in the Commons to deliver a statement on the situation in Ukraine - said: "I welcome the Met's decision to conduct its own investigation because I believe this will help to give the public the clarity it needs and help to draw a line under matters.
"But I want to reassure the House and the whole country that I and the government are focused 100% on dealing with the people's priorities."
The news comes after fresh allegations of a birthday party being held for the prime minister in June 2020.
Downing Street admitted that staff gathered inside No 10 to celebrate Mr Johnson's birthday when the first Covid lockdown was still in place, but ministers have disputed reports about the number of people attending.
Dame Cressida said on Tuesday that she understood the "deep public concern" about the allegations of parties inside No 10, along with the "huge sacrifices" the public had made during the pandemic.
And she said it would "not normally be a proportionate use of time" for the force to investigate rule breaches as far back as two years, but police would look at allegations that "appeared to be the most serious and flagrant breach" of regulations.
Dame Cressida said while the force would not give "a running commentary" on the case, it would provide updates at "significant points".
Liberal Democrat leader Sir Ed Davey told the BBC the government was in "meltdown", adding: "We got here because the prime minister can't tell the truth, he's lied continually, he's been dishonest to Parliament and to the British people.
"He has to go, he should resign."
But Leader of the Commons Jacob Rees-Mogg told reporters the PM's leadership had been "brilliant", and the government had done "an amazing job" throughout the pandemic.
And Tory MP Sir Edward Leigh told MPs: "When Europe stands on the brink of war and there is a cost-of-living crisis, can we please have a sense of proportion over the prime minister being given a piece of cake in his own office by his own staff?"
Boris Johnson says the Met's investigation should bring clarity - but he should perhaps be careful what he wishes for.
We can't anticipate the findings of that inquiry - but even if the prime minister is not slapped with a fixed penalty notice, if any action were to be taken against staff, then questions about the Downing Street "culture" under his leadership will come to the fore.
The former chief whip Mark Harper was anxious to know if the PM himself would be questioned by officers.
Even if this was as a witness, this would not exactly help rebuild the public trust which has eroded in recent weeks.
And the clarity he seeks could take some time to deliver, potentially elongating the political pain.
Some Tory MPs have already openly called for Mr Johnson to go over the alleged parties, but others have said they are waiting to read Ms Gray's conclusions before deciding on the PM's future.
A total of 54 Conservative MPs must write to Sir Graham Brady, chairman of the backbench 1922 Committee, declaring no confidence in the PM, to trigger a leadership contest.
Senior backbench MP David Davis, who called for Mr Johnson to resign at last week's PMQs, said the police investigation meant "this nightmare gets even worse", adding: "We have to be able to get back to dealing with real threats as quickly as possible."
Another senior Tory told the BBC the PM "can't stay now" and this latest development "may trigger a few more to put their letters in".
But a former cabinet minister told the BBC he thought the police investigation would delay more letters being written, adding: "Where it depended on what Sue Gray said, it now depends on what the police will say."
By Daniel Sandford, BBC Home Affairs correspondent
This is a hugely important investigation politically, but as police inquiries go it is actually very straightforward.
It is what is known as a "summary" offence, the maximum penalty is a fine, and if the fine was challenged it would only be dealt with by a magistrates' court.
It would be disproportionate to carry out a very detailed and intrusive investigation.
Now that the Metropolitan Police has decided which of the alleged parties is potentially in breach of the law, the question is: Who was at them?
Much of the leg-work will have been done on that by Sue Gray's team in the Cabinet Office.
Detectives will be looking at emails, CCTV, movements of staff passes, and personal accounts given to Sue Gray or to the police.
They will also be looking at whether anyone who they decide was present at a particular event had a good reason to be there.
It could be that at some of the events some people had a just about good enough reason to be there, but other people did not.
Maybe it was the workplace for some people, and they were just on the right side of the law on that occasion. For others that may not apply.
The government is facing mounting pressure over several events that are alleged to have been held during lockdowns. Here is what we know about them and the restrictions in place at the time:
10 May 2020
Boris Johnson announced a plan to take the “first careful steps" out of the lockdown that began in March 2020. But he said people should continue to "obey the rules on social distancing and to enforce those rules we will increase the fines for the small minority who break them”.
Legal restrictions at the time said you could not leave your house without a reasonable excuse and government guidance was that you could meet one person outside of your household in an outdoor setting while exercising.
15 May 2020
A photo from May 2020 showed the prime minister and his staff with bottles of wine and a cheeseboard in the Downing Street garden. When asked about it, Boris Johnson said, “those people were at work talking about work”.
20 May 2020
About 100 people were invited by email to “socially distanced drinks in the No 10 garden” on behalf of the prime minister’s principal private secretary, Martin Reynolds.
Witnesses told the BBC the PM and his wife were among about 30 people who attended.
Boris Johnson has confirmed he attended the event, saying he was there for 25 minutes and “believed implicitly that this was a work event”.
19 June 2020
On Boris Johnson’s birthday, up to 30 people gathered in the Cabinet Room at No 10 to present the prime minister with a birthday cake and sing Happy Birthday, according to a report by ITV News.
No 10 said staff had “gathered briefly" to "wish the prime minister a happy birthday", adding that he had been there "for less than 10 minutes”.
Rules at the time banned most indoor gatherings involving more than two people.
17 July 2020
Boris Johnson announced plans for a “significant return to normality" in England by Christmas "through targeted, local action” instead of national lockdowns.
But he added that the timetable relied on “every one of us staying alert and acting responsibly”.
5 November 2020
With cases of coronavirus rising again, the prime minister told people in England that “we are once again asking you to stay at home” as a new national lockdown began.
He said people should only leave their homes “for work if you can’t work from home, for education, and for essential activities and emergencies”. Indoor gatherings with other households were banned, unless they were for work purposes.
13 November 2020
Sources told the BBC that Downing Street staff members attended a gathering with Carrie Johnson in the flat where she and the prime minister live. A spokesman for Mrs Johnson denies the party took place.
27 November 2020
A leaving event was held for No 10 aide, Cleo Watson, where people were drinking, and Mr Johnson made a speech, according to sources.
2 December 2020
The second national lockdown ended after four weeks but Boris Johnson replaced those restrictions with “tough tiers to keep this virus down”.
London was placed in tier two, which banned two or more people from different households from meeting indoors, unless “reasonably necessary” for work purposes.
10 December 2020
The Department for Education has confirmed it had an office gathering to thank staff for their work during the pandemic. It says drinks and snacks were brought by those who attended and no outside guests or support staff were invited.
14 December 2020
The Conservative Party has admitted that an “unauthorised gathering” took place at its HQ in Westminster. It was held by the team of the party's London-mayoral candidate, Shaun Bailey, who has since stepped down as chair of the London Assembly police and crime committee. The Metropolitan Police is to speak to two people who attended the party.
15 December 2020
Multiple sources have told the BBC there was a Christmas quiz for No 10 staff last year. A photo - published by the Sunday Mirror - showed Boris Johnson taking part and sitting between two colleagues in No 10. Mr Johnson has denied any wrongdoing.
16 December 2020
London moved into the highest tier of restrictions and Matt Hancock, who was health secretary at the time, said it was important “everyone is cautious” ahead of the festive period.
The Department for Transport apologised after confirming reports of a party in its offices that day, calling it “inappropriate" and an "error of judgment” by staff.
17 December 2020
A leaving party was held at the Cabinet Office for the outgoing head of the civil service Covid taskforce - the team responsible for drawing up coronavirus restrictions.
Kate Josephs, now chief executive of Sheffield City Council, apologised for the event, saying she was “truly sorry that I did this and for the anger that people will feel as a result”.
18 December 2020
Downing Street originally denied a report by the Daily Mirror that a party took place in Downing Street.
However, a video obtained by ITV News showed the prime minister's then-press secretary Allegra Stratton, joking about reports of an event, saying: “This fictional party was a business meeting and it was not socially distanced.”
12 April 2021
Lockdown restrictions were eased in England, with pubs and restaurants allowed to reopen with outdoor service only.
However, working from home continued to be recommended and socialising indoors with people from other households was not allowed. Meeting others outdoors was limited to groups of six people or two households.
16 April 2021
Two parties were held by Downing Street staff at No 10, the night before Prince Philip's funeral.
One of the events was a leaving party for the PM's then director of communications James Slack, who has apologised for the event and acknowledged it “should not have happened at the time that it did”.
Boris Johnson was not at either party.