Smith was the first child of an upper-middle-class family in Glasgow; her father James Smith (1808–1863) was a wealthy architect, and her mother, Janet, the daughter of leading neo-classical architect David Hamilton. The family lived at No 7, Blythswood Square, Glasgow, and also had a country property, "Rowaleyn", near Helensburgh.
Smith broke the strict Victorian conventions of the time when, as a young woman in early 1855, she began a secret love affair with Pierre Emile L'Angelier, an apprentice nurseryman who originally came from the Channel Islands.
The two met late at night at Smith's bedroom window and also engaged in voluminous correspondence. During one of their infrequent meetings alone, she lost her virginity to L'Angelier.
Smith's parents, unaware of the affair with L'Angelier (whom Smith had promised to marry) found a suitable fiancé for her within the Glasgow upper-middle class — William Harper Minnoch.
Smith attempted to break her connection with L'Angelier and, in February 1857, asked him to return the letters she had written to him. Instead, L'Angelier threatened to use the letters to expose her and force her to marry him. She was soon observed in a druggist's office, ordering arsenic, and signed in as M.H. Smith.
Early in the morning of 23 March 1857, L'Angelier died from arsenic poisoning. After Smith's numerous letters were found in his lodging house, she was arrested and charged with murder.
Although the circumstantial evidence pointed towards her guilt (Smith had made purchases of arsenic in the weeks leading up to L'Angelier's death, and had a clear motive) the jury returned a verdict of "not proven", i.e. the jury was unconvinced that Smith was innocent, but the prosecution had produced insufficient evidence to the contrary.
Crucial to the case was the chronology of certain letters from Smith to l'Angelier, and as the letters themselves were undated, the case hinged to some extent on the envelopes. One letter in particular depended on the correct interpretation of the date of the postmark which was unfortunately illegible, and attracted some caustic comments from the judge; but the vast majority of these postmarks were quite clearly struck. It transpired that when the police searched L'Angelier's room, many of Smith's letters were found without their envelopes and were then hurriedly collected and stuck into whichever envelopes came to hand.
The notoriety of the crime and trial were scandalous enough that Smith left Scotland.
On 4 July 1861 she married an artist named George Wardle, William Morris's business manager. They had one son (Thomas) and one daughter (Mary). For a time she became involved with the Fabian Society in London, and sometimes made the coffee at meetings. As she was known by her new married name not everyone knew who she was, but a few did.  After many years of marriage, she and her husband separated, and Madeleine moved to New York City and died in 1928 under the name of Lena Wardle Sheehy.
Most modern scholars believe that Smith committed the crime and the only thing that saved her from the noose was the fact that no eyewitness could prove that Smith and l'Angellier had met in the weeks before his death. 
After the trial, The Scotsman ran a small article stating that a witness had come forward claiming that a young male and female were seen outside Smith's house on the night of l'Angellier's death. However, the trial was already in progress, and the witness could not be questioned during it.
Smith's story was the basis for several plays and the 1950 film Madeleine, directed by David Lean. Jack House's 1961 book Square Mile of Murder, which contained a section on Smith, formed the basis for a BBC television version in 1980. A television play based upon the case, "Killer In Close-Up: The Trial Of Madeleine Smith", written by George F. Kerr, was also produced by Sydney television station ABN-2, airing on August 13, 1958.
The case was an inspiration for Wilkie Collins' 1875 novel The Law and the Lady, though the only main similar feature being the problem of the "not proven" verdict and arsenic poisoning as a means for murder.
Other novels based on the case include The House in Queen Anne's Square (1920) by William Darling Lyell, Letty Lynton (1931) by Marie Belloc Lowndes, Lovers All Untrue (1970) by Norah Lofts, and Alas, for Her That Met Me! (1976) by Mary Ann Ashe (pseudonym of Christianna Brand).
- Dictionary of Scottish Architects: James Smith.
- James Crabb Watt, John Inglis, Lord Justice-General of Scotland: A Memoir (1893), p. 333.
- Knox, William (2006). The lives of Scottish women: women and Scottish society, 1800-1980. Edinburgh University Press. p. 66. ISBN 0-7486-1788-4.
- Richard Davenport-Hines, "Smith , Madeleine Hamilton (1835/6–1928)", Oxford Dictionary of National Biography, Oxford University Press, 2004 accessed 11 April 2008.
- Jack House Square Mile of Murder
- Dougald B. Maceachen, 'Wilkie Collins and British Law', Nineteenth-Century Fiction, Vol. 5, No. 2 (Sep., 1950), pp. 135-138 (University of California Press)
- Campbell, Jimmy Powdrell. Rewriting The Madeleine Smith Story. 2007 ISBN 978-0-7524-4008-8
- Diamond, Michael (2003) Victorian Sensation London: Anthem. ISBN 1-84331-150-X. pp. 172–176
- MacGowan, Douglas. The Strange Affair of Madeleine Smith: Victorian Scotland's Trial of the Century. (Mercat Press, 2007). ISBN 1-84183-113-1.
- MacGowan, Douglas. Murder in Victorian Scotland: The Trial of Madeleine Smith. (1999) ISBN 0-275-96431-0
- House, Jack (1961) Square Mile of Murder. Edinburgh: W. & R. Chambers
- Mackay, James. Scotland's Post (2000) Glasgow
- Hartman, M. S. (1979) "Murder for respectability : The case of Madeleine Smith". Victorian Studies, 16:4, 381-400. Publisher: Indiana University Press.
- Geary, Rick (2006) "A Treasury of Victorian Murder: The Case of Madeleine Smith". New York: NBM.
- Gordon, Eleanor & Nair, Gwyneth (2009) Murder and morality in Victorian Britain: The Story of Madeleine Smith. Manchester: Manchester University Press
- A Most Curious Murder - The Madeleine Smith Story
- The Madeleine Smith Story at the Crime Library
- Madeleine Wardle in later life