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John Constable's The Lock is expected to become one of the most expensive British paintings ever when it is sold at Christie's in London later.
The depiction of rural life in Suffolk is tipped to fetch up to £25 million.
Its owner, Baroness Carmen Thyssen-Bornemisza, said it was "very painful" to sell the 1824 masterpiece but had to because she had "no liquidity".
The work has been housed in Madrid's Bornemisza Museum, one of whose board members has resigned in protest.
Museum trustee Sir Norman Rosenthal criticised the Baroness, known as Tita, for putting one of its prize exhibits up for sale.
In his resignation letter, the former exhibitions director of London's Royal Academy said the decision "represents a moral shame on the part of all those concerned, most especially on the part of Tita".
Constable's six large canvases depicting the area around Flatford Mill in Suffolk changed the course of art.
Pictures such as The Lock might seem a bit traditional now, but in 1824 the artist's use of colour, expressive brushstrokes and contemporary subject was radical.
While The Lock hung in the annual exhibition at the Royal Academy, the Hay Wain - another painting from the series - was being shown at the Paris Salon.
Charles X gave it a gold medal, while artists Théodore Géricault and Eugene Delacroix responded by changing the way they approached painting.
Their Constable-inspired innovations led directly to Impressionism and the birth of modern art.
If it fetches its expected price, The Lock will become one of the five most expensive Old Masters ever sold at auction.
The top price of £49.5m was reached in 2002 by Sir Peter Paul Rubens' painting The Massacre of the Innocents.
A former Miss Spain, the Baroness is the fifth wife and widow of Swiss industrialist Baron Hans Heinrich Thyssen-Bornemisza.
The Lock was part of the huge private art collection he left behind when he died in 2002.
While most of it was sold to Spain, 250 artworks are still in the Baroness' private collection and have been lent to the country free of charge for the past 13 years.
Announcing the sale of the Constable painting in May, the Baroness said she needed to sell because of the current economic crisis.
"It's very painful for me, but there was no other way out," she told the Spanish newspaper El Pais. "I need the money, I really need it. I have no liquidity.
"Keeping the collection here is costly to me and I get nothing in return."
Francesca Von Habsburg, the Baroness's stepdaughter and another museum board member, has also expressed disapproval over the sale.
"The baroness has shown absolutely no respect for my father and is simply putting her own finanical needs above everything else," she told The Mail on Sunday.
The top end of the art market has escaped many of the problems faced by the wider global economy, with new records consistently being set for individual artists.
Last month Joan Miro's 1927 work Peinture (Etoile Bleue) sold for more than £23.5m, a record for the Spanish painter.
In May Edvard Munch's The Scream became the most expensive art work ever sold at auction, selling for $119.9m (£74m) in New York.
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