Samuel Sotheby's uncle, John Sotheby (1740–1807), was partner and nephew of Samuel Baker, who founded at York Street, Covent Garden, in 1744 the first English sale-exclusively for books, manuscripts, and prints.
After 1803, and until the death of Leigh in 1815, the firm carried on their business at a new address, 145 Strand.
John Sotheby died in 1807, and on Leigh's death, eight years later, Samuel continued the concern by himself, moving to 3 Waterloo Street, Strand, about 1817.
After a visit to the Netherlands in 1824 to examine specimens at Haarlem for his friend William Young Ottley, his attention was first specially directed to block books.
His collections were edited by his son as The Typography of the Fifteenth Century, 1845, and Principia Typographica, 1858, 3 vols.