The doctors suggested it would fragment services, possibly threatening vaccination and screening campaigns.
But the government insisted the reforms would improve the health service.
The revelation that such influential members of the public health community have put their names to the letter comes on the day Health Secretary Andrew Lansley is to address the Conservative Party conference.
Concessions The NHS reforms have been one of the most controversial areas of government policy over the past year.
The proposals even had to be put on hold in the spring amid mounting criticisms from the medical profession, academics and MPs.
It led to ministers making a number of concessions. These included giving health professionals other than GPs more power over how NHS funds are spent as well as watering down the role of competition.
But the intervention by the public health experts illustrates there is still widespread opposition - despite claims by the prime minister last month that the NHS now backed the changes.
Signatories include Sir Michael Marmot, one of the world's leading experts on health inequalities, and 26 directors of public health.
The letter, which has been sent to members of the House of Lords, states: "The bill will do irreparable harm to the NHS, to individual patients and to society as a whole."It goes to say that the increased commercialisation and marketisation would "fragment patient care, aggravate risks to individual patient safety... and undermine the ability of the health system to respond effectively and efficiently to communicable disease outbreaks and other public health emergencies".
It adds: "The government claims that the reforms have the backing of the health professionals. They do not. Neither do they have the general support of the public."
Inner north-west London public health chief Dr David McCoy, who has signed the letter, said the impact could be felt in vital areas of public health such as "vaccination, TB control and cancer screening".
"Healthcare requires a co-ordinated and collaborative approach," he added.
The criticisms follow on from warnings from other groups, such as the Royal College of Nursing and British Medical Association, about the damage the changes may cause.
Shadow health secretary John Healey said: "David Cameron is in denial, both about the damage his plans are doing to the NHS and the strength of opposition."
A Department of Health spokesman said the overhaul represented a "once in a lifetime opportunity" to improve the system.
He added: "We are very disappointed that these individuals, who pride themselves in the use of evidence, should have fallen back into such generalised assertions for which there is not one shred of evidence."
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