Born in Sheffield, Smithers worked as a solicitor, qualifying in 1884, and became friendly with the explorer and orientalist Sir Richard Francis Burton. He published Burton's translation of the Book of One Thousand and One Nights in 1885. He collaborated with Burton in a translation from the Latin of the Carmina of Caius Valerius Catullus and Priapeia, a collection of erotic poems by various writers. He also published a limited edition of the Satyricon of Petronius Arbiter.
Smithers published works by Aubrey Beardsley, Max Beerbohm, Aleister Crowley, Ernest Dowson, Arthur Symons and Oscar Wilde and lesser known figures such as Vincent O'Sullivan and Nigel Tourneur. With Symons and Beardsley, he founded The Savoy, a periodical which ran to eight issues in 1896. In partnership with Harry Sidney Nichols, he published a series of pornographic books under the imprint of the "Erotika Biblion Society": He was notorious for posting a slogan at his bookshop in Bond Street reading "Smut is cheap today".
When Beardsley converted to Roman Catholicism, he asked Smithers to “destroy all copies of Lysistrata and bad drawings...by all that is holy all obscene drawings." Smithers ignored Beardsley's wishes and continued to sell reproductions as well as forgeries of Beardsley's work.
He went bankrupt in 1900, and died in 1907 from cirrhosis of the liver. His body was found in a house in Parson's Green on his 46th birthday, surrounded by empty bottles of Dr J. Collis Browne's Chlorodyne. He was buried in an unmarked grave, paid for by Lord Alfred Douglas, in a cemetery in Fulham Palace Road.
- Leonard C. Smithers and Sir Richard Burton. Priapeia sive diversorum poetarum in Priapum lusus or Sportive Epigrams on Priapus by divers poets in English verse and prose. 1890 .
- James G. Nelson, Publisher to the Decadents: Leonard Smithers in the Careers of Beardsley, Wilde, Dowson. Rivendale Press, May 2000. ISBN 0-953503-38-0
- John Sutherland, "The Stanford Companion to Victorian Fiction", Stanford University Press, 1990, ISBN 0-8047-1842-3, p. 591.
- Bruce S. Harris (ed.), "The Collected Drawings of Aubrey Beardsley", Crown Publishers, 1967, p.v
- Rachel Potter, "Obscene Modernism and the Trade in Salacious Books", Modernism/modernity, Volume 16, Number 1, January 2009, pp. 87–104 doi:10.1353/mod.0.0065 
- Matthew Sweet, Inventing the Victorians, Faber and Faber, 2001, ISBN 978-0-571-20663-6