The "T-charge" will apply to drivers whose vehicles do not meet Euro 4 emission standards - typically petrol and diesel cars registered before 2006 - in the latest move by the mayor to crack down on air pollution.
Up to 10,000 vehicles each weekday are expected to face the charge, which will operate on top of and during the same times as the congestion charge, so it will cost £21.50 to drive a pre-Euro 4 vehicle in the central London zone at those times.
Air pollution is linked to 9,000 early deaths a year in London, one of many places hit by the UK's air quality crisis, which has prompted the European Commission to issue a "final warning" to the government for repeated breaches of legal limits.
One road in the capital exceeded its allowed annual levels of nitrogen dioxide just five days into 2017.
Pollutants - much of which come from traffic, particularly diesel vehicles - cause health problems such as asthma, heart and lung diseases.
They are also thought to affect children's health and development.
The charge will be introduced on October 23, at the start of the autumn half-term, and will be in operation Mondays to Fridays, 7am to 6pm.
Mr Khan said: "It's staggering that we live in a city where the air is so toxic that many of our children are growing up with lung problems.
"If we don't make drastic changes now we won't be protecting the health of our families in the future."
He said the T-charge was the "toughest emission standard of any major city" and was overwhelmingly backed by Londoners because they wanted immediate action to tackle air pollution.
The charge is a step to bringing in the world's first "ultra-low emission zone", which will charge more polluting cars. It could come in as early as 2019 and may be extended from central London to the north and south circular roads, he said.
Mr Khan also repeated his call for the government to bring in a national diesel scrappage fund and a new Clean Air Act to address pollution.
James Thornton, chief executive of law firm ClientEarth, which has taken the government to the Supreme and High Courts over air pollution, said: "The T-charge is absolutely essential to protect human health in the short-term and pave the way for the mayor's expanded ultra-low emission zone, but needs to go further and be applied to more diesel vehicles.
"The High Court made it crystal clear that protecting human health must take top priority - so the government should be working with the mayor to speed up policies and mitigate the impacts on drivers and small businesses through a scrappage scheme and other fiscal policies - not holding him back."
Watch activists climb Nelson's Column in Greenpeace pollution protest for cleaner air in the capital last year
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