Offers in excess of £4m are being sought for the plot next to Chorlton High School on Mauldeth Road West.
Owned by PJD Holdings, the 1.7-acre Chorlton site is occupied by the 27,000 sq ft Lowry House office building that was most recently used by the school.
Located within a predominately residential area, the site is close to Barlow Moor Road Metrolink station and Chorlton Park.
Manchester agencies Edwards & Co and Canning O’Neill are advertising the site for sale.
Andrew Timms, director at Edwards & Co, said: “Located in one of the most desirable neighbourhoods in South Manchester, Lowry House provides a rare opportunity to purchase a site of this size with vacant possession.
“The efficient layout of the property lends itself well for conversion or development and we expect considerable interest from a variety of parties.”
Best offers are to be submitted before the end of the month.