The mayor said he took the action, in his role as chair of the London Resilience Forum, as the situation was now “critical, with the spread of the virus out of control”.
Hospitals in London are “at risk of being overwhelmed”, with beds likely to run out within the next two weeks unless the spread of the virus slows dramatically, he said.
Declaring a major incident allows authorities to step up the co-ordinated emergency response to crisis situations involving serious risk to human life and welfare, and gives additional weight to requests for assistance from central government. The measure was previously invoked for the Grenfell Tower fire and Westminster Bridge and London Bridge terror attacks.
With one Londoner in 30 - and one in 20 in some parts of the city - now infected with Covid-19, the pressure on health services has become increasingly intense in the past weeks.
The mayor wants to ram home the seriousness of the situation and the need for Londoners to obey lockdown requirements to stay home and avoid mixing.
And police warned they are ready to impose fines on those creating “breeding grounds” for the virulent new variant of Covid by holding parties and raves in defiance of stay-home orders.
Between 30 December and 6 January, the number of patients in London hospitals grew by 27 per cent (from 5,524 to 7,034) and the number on mechanical ventilation grew by 42 per cent (from 640 to 908).
Over the last three days alone, the NHS has announced 477 deaths in London hospitals following a positive test for Covid-19.
The 7,034 people currently in hospital with Covid-19 represents a 35 per cent increase compared to the peak of the pandemic in April. There are currently around 830 admissions to London hospital trusts per day – up from around 500 before Christmas - with the London Ambulance Service taking up to 8,000 emergency calls a day now, compared to 5,500 on a typical busy day.
Mr Khan consulted with leaders of NHS London, local authorities, Public Health England and the emergency services before taking the step.
He said: “The number of cases in London has increased rapidly with more than a third more patients being treated in our hospitals now compared to the peak of the pandemic last April.
"Our heroic doctors, nurses and NHS staff are doing an amazing job, but with cases rising so rapidly, our hospitals are at risk of being overwhelmed. The stark reality is that we will run out of beds for patients in the next couple of weeks unless the spread of the virus slows down drastically.
“We are declaring a major incident because the threat this virus poses to our city is at crisis point. If we do not take immediate action now, our NHS could be overwhelmed and more people will die.
“Londoners continue to make huge sacrifices and I am today imploring them to please stay at home unless it is absolutely necessary for you to leave. Stay at home to protect yourself, your family, friends and other Londoners and to protect our NHS.”
The chair of London Councils, Georgia Gould, said: “Cases are rising at a dangerous rate in London, putting extreme pressure on the NHS.
“One in 30 Londoners now has Covid. This is why public services across London are urging all Londoners to please stay at home except for absolutely essential shopping and exercise.
“This is a dark and difficult time for our city but there is light at end of the tunnel with the vaccine rollout. We are asking Londoners to come together one last time to stop the spread - lives really do depend on it.”
Deputy Assistant Commissioner Matt Twist, who leads the Metropolitan Police response to the Covid pandemic, described the “major incident” decision as “a stark reminder of the critical point we are at”.
“There can be no doubt that right now we find ourselves at a serious and dangerous crossroads for London,” said Mr Twist.
"Everyone must look at this news and understand that our health service is nearing breaking point. I know Londoners will be shocked that officers are still dealing with a small selfish minority who think the rules don't apply to them by holding house parties, large warehouse raves or other gatherings. These are creating breeding grounds for the much more transmissible variant.
"These rule breakers cannot continue to feign ignorance of the risk that this virus poses or listen to the false information and lies that some promote downplaying the dangers. Every time the virus spreads it increases the risk of someone needlessly losing their life.
"Earlier this week the Met issued refreshed instructions to officers to issue fines more quickly to anyone committing obvious, wilful and serious breaches. That is happening and it will continue to happen."
Register for free to continue reading
Registration is a free and easy way to support our truly independent journalism
By registering, you will also enjoy limited access to Premium articles, exclusive newsletters, commenting, and virtual events with our leading journalists
Already have an account? sign in
Join our new commenting forum
Join thought-provoking conversations, follow other Independent readers and see their replies