Peter Palumbo has put Mies van der Rohe's seminal Farnsworth House up for sale in a Sotheby's auction set for 12 December.
The decision follows the collapse of proposals that would have seen Chicago authorities buy the 1951 house and guarantee its upkeep.
Palumbo - who bought the house from original owner Dr Edith Farnsworth in 1972 - has spent the past 30 years renovating it to its original condition. In recent years it opened to the public.
He had agreed to sell it to the City of Chicago as a way of preserving its surroundings and preventing additions. However, a 'severe crisis' in the city's finances means it can no longer proceed.
The one-storey house - which is expected to raise $6-7million (£3.6-4.2 million) - is described by Sotheby's senior vice-president James Zemaitis as 'Mies' most successful application of his 'less is more'motto'.
'The Farnsworth House is one of the seven wonders of the Modern architectural world, ' Zemaitis added, 'and it rightly takes its place alongside Frank Lloyd Wright's Fallingwater as one of the most recognisable icons of the American Modernist landscape.'
Lord Palumbo puts Farnsworth up for sale after city deal collapses