A revised plan has now been drawn up for the 80-hectare former gasworks site being developed by Knight Dragon.
Over 12,000 homes will create a new district formed of five neighbourhood zones.
Works on the site, taken on by the mayor in 2012, previously stalled after a similar plan was granted planning permission in 2004.
Nearly 3,000 homes are currently being developed on the site, bringing the total housing delivery on the Greenwich Peninsula to 15,720.
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Further plans also include 220 serviced apartments, 24,000 sq m of retail use, 60,000 sq m of business use, two new schools and two new hotels.
In addition, a 40,000 sq m film studio, a visitor attraction and increased green open spaces will be built, along with an extension to the existing Central Park.
Greenwich Council gave outline planning permission for the site in August.
The Mayor said: "This gigantic site at Greenwich Peninsula has sat dormant for far too long, so I'm pleased that since City Hall took control of this land, we are already beginning to see construction underway.
"This will not only provide thousands of much-needed new homes for Londoners, but also bring jobs as part of the wider regeneration towards the east of the capital."
Richard Margree, Chief Executive of Knight Dragon, added: "The continued support of the Mayor and his team has given us the confidence and ambition to start the transformation of London's biggest regeneration site."
(LM/JP)
