Berkeley Group subsidiary St William is preparing for a major clean-up operation across the derelict east London site ahead of construction starting on the first homes.
The hybrid masterplan was called in by City Hall in April after Newham Council approved the initial phase last year.
Mayoral approval now allows St William to move forward with plans for thousands of homes, a five-acre riverside park, 5,000 sq m of mixed-use space and a new DLR station.
The first phase will feature buildings reaching up to 15 storeys in height.
St William will also undertake an extensive programme of remediation and enabling works to prepare the heavily contaminated former gasworks site for redevelopment.
Initial works will cover approximately 30 acres of land, which has remained derelict since gas production ended in the 1960s.
Berkeley is expected to invest around £250m in site preparation, infrastructure and remediation works before the wider residential development can progress.
The scheme has attracted scrutiny over its initial affordable housing provision, which stands at around 8%, while the development will also lead to the loss of protected habitat.
Construction could begin in 2028, with the first homes expected to be completed from 2030.
Dean Summers, managing director of St James & St William, said: “This marks a significant step forward for this complex, long-term regeneration site.”