Samuel Leigh Sotheby was born on 31 August 1805. He entered the family business; the third (and last) generation of Sotheby's involved in the auction house.
When the library of Georg Kloss, doctor and collector of incunabula and early printed books, was sent for sale in 1835, Sotheby prepared the collection for auction.
In his auction catalogue, he claimed that the Kloss collection contained the library of 16th century humanist and reformer Philipp Melanchthon and placed considerable emphasis on the annotations found in the books and manuscripts.
Kloss had in fact connected only a few items with Melanchthon, and made a vigorous stand against what he saw as Sotheby's excessive claims regarding his library's provenance.
In 1840, Sotheby attempted further justification of his opinion in a monograph entitled "Unpublished Documents, Marginal Notes, and Memoranda in the Autograph of Philip Melanchthon and of Martin Luther, with numerous facsimiles, accompanied with Observations upon the varieties of style in the Handwriting of those Illustrious Reformers".
He drowned in the River Dart near Buckfastleigh, Devon on 19 June 1861, and is buried in Brompton Cemetery.