The hospital will be a base for planned surgery and community services
An accident and emergency department will close at a south-east London hospital by 2011, it was confirmed.
Queen Mary's Hospital, Sidcup, will also lose its maternity unit under plans approved by the government.
A South London Healthcare NHS Trust spokesman said the move would enable it to "concentrate our resources".
But protesters said they must travel further for treatment as a result. The trust had faced a projected shortfall of £200m in its finances next year.
Secretary of State for Health Alan Johnson approved the plan for south-east London health services in Bexley, Bromley, Greenwich and Lewisham on Friday.
Queen Mary's Hospital will lose its A&E department, obstetrics unit and children's inpatients service within the next two years.
Instead it will specialise in planned surgery and become a base for community healthcare services.
The hospital's Urgent Care Centre services, which the trust says can treat the majority of A&E patients, will be extended to 24 hours.
Hospital's A&E closure approved
A&E services will remain at Princess Royal University Hospital in Bromley, Queen Elizabeth Hospital in Greenwich and University Hospital Lewisham.
Last year hundreds of campaigners held a candlelit vigil in protest against the "downgrading" of Queen Mary's Hospital.
But South London Healthcare NHS Trust medical director Roger Smith said the move would "make better use of our staff and provide better services".
"One of the things that will happen is that we can concentrate our resources into slightly fewer units - at the moment we are spread very thinly across our four sites," he said.
"There will be changes at Queen Mary's but I think the main implications of these changes will be that healthcare for the population of south-east London will be much improved."
Mr Smith said the trust was "certainly not contemplating making anyone redundant" as a result of the changes.