The former Manchester United stars want to build a tower block in their home city including apartments, offices, restaurants and a five-star hotel.
The 20th Century Society has asked for the Manchester Reform Synagogue to be "listed" to block the players' Â£200m St Michael's development on Jackson Row.
Historic England will assess whether to give it Grade II listed status.
The 1953 synagogue would be bulldozed and rebuilt on the site close to Manchester Town Hall under plans to be submitted later this year.
The 19th Century Sir Ralph Abercromby pub and the former Bootle Street police station also face being demolished.
Tess Pinto, the 20th Century Society's conservation advisor, told the BBC: "We are worried about these plans in particular because the site contains three interesting and beautiful historic buildings.
"And in their place they want to put up 31-storey skyscrapers which will have a serious impact on Manchester's skyline."
However the Jewish congregation support plans for a new synagogue as the old one is "damp and outdated" with limited parking.
An Historic England spokeswoman said: "The planning decision would still be up to the council.
"However it is unusual for listed building to be knocked down."
Charity campaigners have applied to save a synagogue from being flattened by Ryan Giggs and Gary Neville.