The mayor of London said: “The Omicron variant has quickly become dominant with cases increasing rapidly and the number of patients in our hospitals with Covid-19 on the rise again.”
The number of Covid-19 cases in London has rapidly increased, with 65,525 new confirmed cases in the past seven days.
In the last 24 hours alone, 26,418 cases have been reported – the highest number since the start of the pandemic.
And in the last week, the number of Covid-19 patients in London hospitals has gone up 29% - the largest rise in England.
Mr Khan said: “The surge in cases of the Omicron variant across our capital is hugely concerning, so we are once again declaring a major incident because of the threat of Covid-19 to our city.
“The Omicron variant has quickly become dominant with cases increasing rapidly and the number of patients in our hospitals with Covid-19 on the rise again.
“We are already feeling the impact across the capital and while we are still learning about this variant, it’s right that London’s key agencies work closely together to minimise the impact on our city, including helping to protect the vital vaccination programme.”
A major incident is defined as an event or situation with a range of serious consequences, which requires special arrangements to be implemented by one or more emergency responder agency.
The mayor’s office said “it is likely to involve serious harm, damage, disruption or risk to human life or welfare, essential services, the environment or national security.”
A strategic coordinating group will be established, to better link together public services to tackle the spread of the Omicron variant.
The mayor’s office said this will have a government representative on it, to allow faster dialogue with Number 10 and key departments.
Sadiq Khan previously declared a major incident on January 8 due to high Covid rates, but was able to stand it down on February 26.
Other major incidents have included the Grenfell Tower fire in June 2017, the terror attacks at Westminster Bridge and London Bridge and the Croydon tram crash in November 2016.
And with London also having some of the lowest vaccination rates in the country, Mr Khan urged people to get their booster jabs.
“We know that the vaccine offer our best defence against the virus,” he said.
“There are now more clinics in London delivering vaccines than at any point during the pandemic.
“I urge all Londoners to book their appointment or to go to one of the many walk-in centres across the capital as soon as you can.”
Georgia Gould, chair of London Councils, said: “The rapid spread of Omicron across our city is of huge concern.
“Local councils have stepped up and played a vital role in supporting their communities through the pandemic, I know they will continue with these efforts but we cannot do this alone.
“Vaccines offer the best protection against the virus and now more than ever it’s important that Londoners take up the offer to get a booster as soon as possible.
If you’ve not had your first and second dose yet, please do come forward and protect yourselves and others around you.
“Together we must do all we can to defeat this virus.”