The 605-home Old Oak and Park Royal regeneration project in west London was initially set to feature 200 affordable homes.
However, the mayor of London and developer Genesis Housing Association (GHA) have now agreed to raise this number to 242.
Neil Hadden, chief executive at GHA, said: “We are delighted that the redevelopment at Oaklands, in one of Hammersmith and Fulham’s most important regeneration sites, has been approved.
“We will now be able to provide hundreds more affordable homes for Londoners on a once derelict site.
“Partnerships such as the one we have with QPR enable us to invest, not only in building new homes, but in developing new communities.”
Half of the 242 homes will be for social and affordable rent, while the other half will be for shared ownership.
Greater London Authority (GLA) Affordable Housing Grant will help to fund the extra homes.
The GLA has also implemented a review mechanism to ensure that any surplus profit will be reinvested to raise the total to 50% affordable homes.
The mayor’s office claimed that Old Oak and Park Royal has the potential to deliver 25,500 new homes and 65,000 jobs over the next 30 to 40 years.
The site will also become the key transport interchange for Crossrail and HS2.
Mr Khan added: “The scale and ambition for this development shows London is very much open for business.
“Despite the uncertainty caused by the UK’s vote to leave the European Union, it remains clear that developers and investors see long-term potential in our great city.”
Tony Fernandes, co-chairman of QPR, said: “We are delighted that the mayor has granted planning permissions for the Oaklands development, including hundreds of affordable homes for Londoners.
“Along with our development partners Genesis Housing Association we look forward to creating this new neighbourhood, building a sustainable community where people can live, work and play.
“We are committed to bringing forward other development sites in Old Oak as soon as possible to create the homes that London desperately needs.”