Developer Lend Lease is set to start work on the Trafalgar Place element of the £1.5 billion regeneration of Elephant & Castle's Heygate Estate.
Project director Pascal Mittermaier said that the start this week of the 235-home scheme was "another decisive step" in the area’s transformation.
The whole programme is expected to see the construction of up to 3,000 new homes over the next 15 years, as well as new shops, restaurants, community facilities and public spaces.
Work has already started on Lend Lease’s 284-home, 37-storey One The Elephant tower.
An art gallery dedicated to science has launched its first exhibition after opening in September.