The London Ambulance Service (LAS) has said it expects to make 890 job cuts over the next five years as part of an attempt to reduce costs.
The LAS, which is trying to save £53m over five years, said 300 staff left each year so most reductions should come from "natural wastage".
The LAS, which employs about 5,000 people, said the cuts would include 560 frontline jobs.
Public sector union Unison warned the cuts were "so deep they may not heal".
The government says it is investing an extra £12bn in the NHS, while savings will be reinvested in patient care.
LAS chief executive Peter Bradley said: "All areas of our business will face closer scrutiny as we look for ways to make savings while improving the care we give to patients.
"But with nearly 80% of our budget spent on staff costs it would be impossible to make the savings required without removing posts."
"Unfortunately we are not immune to financial pressures facing the NHS."
A further 330 posts will be removed from management and support services.
Unison's regional organiser, Phil Thompson, said: "This is being forced on the service by the government.
"These cuts are so deep they may not heal.
"If allowed to be carried out they will put at risk the many Londoners who rely on the LAS every day."
London Ambulance Service worker Eric Roberts, a Unison official, added: "I am shocked by the size of these cuts. This is a cull of highly-trained staff."
The Department of Health responded with a statement from NHS chief executive Sir David Nicholson.
He said: "It is critical the NHS uses efficiency savings to make real improvements in the quality of care for patients.
"There is no excuse to reduce services for patients when the NHS will receive an extra £11.5 billion of funding.
"Every penny saved from measures taken to reduce costs will be reinvested in patient care."
LAS deals with more than 1.5m emergency calls each year, visiting over 1m incidents.
Last year the number of call-outs rose by 4.5%.