A report into the impact of a proposed building project on Liverpool's historic waterfront said it would leave the area "irreversibly damaged".
Unesco inspectors visited the city in November to investigate the impact of the Liverpool Waters development on its world heritage site.
Their report said the scheme would cause a "serious loss of historical authenticity".
Council leader Joe Anderson said the scheme was "vital to our prosperity".
The visit by Unesco considered the plans submitted by Peel Holdings for the £5.5bn Liverpool Waters - which includes offices, shops and restaurants - and the management of the city's Maritime Mercantile City world heritage site.
The site includes much of the city's famous waterfront, including the Three Graces - the Royal Liver Building, the Cunard Building and the Port of Liverpool Building - the Pier Head, the Albert Dock and the Stanley Dock Conservation Area.
The report said that while the scheme had yet to be "properly designed", it would cause "a serious deterioration of [Liverpool's] architectural and town-planning coherence, a serious loss of historical authenticity and an important loss of cultural significance".
It added that a Peel Holdings report into the development had also indicated that "several key views from the north will be blocked by the new developments, while also the hard-won views of the Three Graces from Kings Dock will disappear against a backdrop of supertowers".
The report concluded by saying that Unesco "strongly recommends that the three principal stakeholders - Liverpool City Council, Peel Holdings and English Heritage - reconvene and work out an adjusted scheme".
It said that while the UN cultural body was "fully supportive of the regeneration efforts undertaken by the city council, it will not support the Liverpool Waters scheme in its current outline, as it will be developed at the expense of the city's heritage and its outstanding universal value".
Mr Anderson, the leader of the city council, said he had "always believed there is a way forward which will allow us to redevelop the North Liverpool Docks and secure the massive investment and badly-needed new jobs, and to also preserve our World Heritage status".
"Peel have already made significant alterations to their proposals since drawing up the original plans," he said.
"The plans are vital for the future of what is one the poorest parts of the country and the investment is vital to our city's future prosperity.
"However, we are mindful of the need to build a better future for our city in a careful and sensitive way."
A spokeswoman for English Heritage said that as a "statutory advisor to Liverpool City Council", the charity would be willing to reconvene "if invited".
"We believe that a revised scheme for the central docks could reduce the amount of harm to the site and deliver long-term benefits, which include jobs and growth but also the repair and re-use of historic buildings," she said.
Peel Holdings declined to comment.