The historic artwork depicts the moment where Admiral Lord Nelson was fatally wounded at the battle of Trafalgar in 1805.
It will go on sale at The Chelsea Antiques & Fine Art Fair in London, priced at £350,000.
The mural, titled ‘Lord Nelson’s Victory of Trafalgar’, is being sold by art dealer Martyn Downer.
Mr Downer said the painting was created by Mather Brown, a Boston-born American artist (1761-1831) who knew Lord Nelson while in London.
The art dealer said the piece is an exciting prospect for collectors.
He added: ‘Mather Brown was one of a small group of artists – such as his fellow American Benjamin West, who were well known to Nelson in London.
‘That familiarity is evident in Brown’s vivid and theatrical representation of Nelson receiving his fatal wound at the battle of Trafalgar which, amid the smoke of conflict, offers us one of the most compelling and well-informed late portraits of the admiral.
‘The re-discovery of Brown’s bold attempt to win the 1805 competition for the best painting of the dramatic scene is an exciting moment for Nelson enthusiasts and for scholars of eighteenth-century art, especially for followers of this fascinating and complex artist.’
After originally being sold to former mayor of Liverpool, John Bridge Aspinall, in 1804, the painting has changed hands several times among private owners.
It is now the major attraction of the The Chelsea Antiques & Fine Art Fair, running from March 23 to March 27.
Other Lord Nelson memorabilia will also be sold, including Lady Hamilton’s keepsake ‘orange blossom’ box, used to contain her wedding flowers.
It has a ticket price of £6,600.
More information about the antiques fair can be found here.