Battersea Power Station Development Company boss Rob Tincknell has resigned after 10 years leading the £8bn development.
Chief executive Mr Tincknell will leave the company in the summer but retain an advisory role on the project board.
Current chief financial officer and deputy CEO Simon Murphy will take over on a permanent basis from 1 May.
Mr Tincknell said: “After 10 years as CEO of this extraordinary project, leaving has been a difficult decision for me.
“I hand over to Simon knowing the fantastic team we’ve built here will take the development forward in a way which continues to make us all proud and deliver for London.
“I would like to thank the Malaysian shareholders for their unstinting commitment and support over the years, Battersea would certainly not be happening without them.
“I look forward to continuing to support the project and the shareholders as a member of the advisory board.”
He told the Evening Standard that “things are stable” on the project and that after a decade on the job “it’s the right time for me to do other things”.
Battersea Power Station Development Company chairman Dato’ Johan Ariffin said giving the top job to Mr Murphy, who has worked on the project since 2012, would ensure a “smooth transition”.
“Simon and all of Team Battersea have our full and unanimous support,” he said.
“We look forward to continuing to work together in developing and successfully executing the ongoing strategy for this iconic development.”
In January two Malaysian investors took full control of Battersea Power Station, increasing their investments from 70 to 100 per cent.
The move was said to “ensure delivery of the building”, which will house Apple’s UK HQ when the redevelopment is completed in 2020.
Last year the project hit two hurdles when a dispute with Transport for London emerged over who should pay for a new tube station at the site.
Then in the summer Skanska end its work on phase two of the scheme in the summer. Mace are now completing the job.