The firm has agreed to secure planning and develop the Silvertown Way project in Canning Town.
Proposals include building over 1,100 mixed tenure homes across a series of individual blocks.
The scheme has a gross development value of £380 million, making it the largest housing scheme Galliford has undertaken.
The project will be delivered through an existing joint venture (JV) agreement with Thames Valley Housing Association (HA).
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It is understood a third of the homes will be for private market rent, through Thames Valley's subsidiary Fizzy Living.
Approximately 380 affordable homes will be developed for London and Quadrant HA.
The company's housebuilding businesses, Linden Homes and Galliford Try Partnerships, will be responsible for undertaking the project.
Features include a hotel, restaurant, employment and commercial space alongside the new homes.
Executive Chairman, Greg Fitzgerald, said: "I am delighted that we have been able to work with all the stakeholders involved in this project to reach an agreement, and deliver much-needed new homes for London.
"As well as being a hugely significant project for our company, Silvertown Way will be a flagship regeneration project for East London, and we are committed to providing high-quality housing of all tenures for the local community."
(LM)
