Matthew Gregory Lewis was the firstborn child of Matthew and Frances Maria Sewell Lewis. His father, Matthew Lewis was the son of William Lewis and Jane Gregory. He was born in Jamaica in 1750. He attended Westminster School before proceeding to Christ Church, Oxford, where he received his bachelor’s degree in 1769 and his master’s in 1772. That same year, he was appointed as the Chief Clerk in the War Office. The following year, Lewis married Frances Maria Sewell, a young woman who was very popular at court. She was the third daughter born to Sir Thomas Sewell and was one of eight children born in his first marriage. Her family, like Lewis’, had connections with Jamaica. As a child, she spent her time in Ottershaw. In December 1775, in addition to his post as the Chief Clerk in the War Office, Lewis became the Deputy - Secretary at War. With one exception, he was the first to hold both positions at that same time (and earning both incomes). Lewis owned considerable property in Jamaica, within four miles of Savanna - la - Mer, or Savanna - la - Mar, which was hit by a devastating earthquake and hurricane in 1779. His son would later inherit this property.

In addition to Matthew Gregory Lewis, Matthew and Frances had three other children: Maria, Barrington, and Sophia Elizabeth. On 23 July 1781, when Matthew was six and his youngest sister was one and a half years old, Frances left her husband, taking the music master, Samuel Harrison, as her lover. During their estrangement, Frances lived under a different name, Langley, in order to hide her location from her husband. He still, however, knew her whereabouts. On 3 July 1782, Frances gave birth to a child. That same day, hearing of the birth, her estranged husband returned. Afterwards, he began to arrange a legal separation from his wife. After formally accusing his wife of adultery through the Consistory Court of the Bishop of London on 27 February 1783, he petitioned the House of Lords for permission to bring about a bill of divorce. However, as these bills were rarely granted, it was rejected when brought to voting. Consequently, Matthew and Frances remained married until his death in 1812. Frances, though withdrawing from society and temporarily moving to France, was always supported financially by her husband and then later, her son. She later returned to London and then finally finished her days at Leatherhead, rejoining society and even becoming a lady - in - waiting to the Princess of Wales. Frances and her son remained quite close, with her taking on the responsibility of helping him with his literary career. She even became a published author, much to her son’s dislike.

Matthew Gregory Lewis began his education at a preparatory school under Reverend Dr. John Fountain, Dean of York at Maryleborne Seminary, a friend of both the Lewis and Sewell families. Here, Lewis learned Latin, Greek, French, writing, arithmetic, drawing, dancing, and fencing. Throughout the school day, he and his classmates were only permitted to converse in French. Like many of his classmates, Lewis used the Maryleborne Seminary as a stepping stone, proceeding from there to the Westminster School, like his father, at age eight. Here, he acted in the Town Boys’ Play as Falconbridge in King John and then My Lord Duke in High Life Below Stairs. Later, again like his father, he began studying at Christ Church, Oxford, on 27 April 1790 at the age of fifteen. He graduated with a bachelor’s degree in 1794. He later earned a master's degree from the same school in 1797.

In 1791, he sent his mother a copy of a farce that he had written named The Epistolary Intrigue. Though he intended the play to be performed at London’s Drury Lane, it was rejected there and then later by the neighboring Covent Garden. Supposedly, during this time, he also completed a two volume novel. However, today this novel only exists in fragments in the posthumously published work The Life and Correspondence of M.G. Lewis. In March 1792, Lewis translated the French opera Felix and sent it to Drury Lane, hoping to earn money for his mother. While he tried to write a novel like Horace Walpole’s The Castle of Otranto, he mainly adhered to theatre, writing The East Indian, but seven years elapsed before it appeared onstage at Drury Lane. In Germany, he even translated Wieland’s Oberon, a difficult work of poetry which earned him the respect of his acquaintance Johann Wolfgang von Goethe.

While Lewis pursued these literary ambitions, mainly to earn money for his mother, his father’s influences secured him the position as an attaché to the British embassy in The Hague. He arrived on 15 May 1794 and remained until December of the same year. Though finding friends at the local pubs (his favorite being Madame de Matignon’s Salon) amongst visiting French aristocracy who were fleeing revolutionary France, Lewis saw The Hague as boredom’s home, disliking the city’s Dutch citizens. It was here that he produced, in ten weeks, his romance Ambrosio, or The Monk which was published anonymously in the summer of the following year. It immediately achieved celebrity for Lewis. However, some passages in the work were of such a nature that about a year after its appearance, an injunction to restrain its sale (a rule nisi) was obtained. In the second edition, Lewis, in addition to citing himself as the author and as a Member of Parliament, removed what he assumed were the objectionable passages, yet, the work retained much of its horrific character. Lord Byron in English Bards and Scotch Reviewers wrote of "Wonder - working Lewis, Monk or Bard, who fain wouldst make Parnassus a churchyard; Even Satan's self with thee might dread to dwell, And in thy skull discern a deeper hell." The Marquis de Sade also praised Lewis in his essay "Reflections on the Novel".

Whatever its weaknesses, ethical or aesthetic, may have been, The Monk did not interfere with the reception of Lewis into the best society; he was favourably noticed at court, and almost as soon as he came of age, in 1796, he obtained a seat in the House of Commons as a Whig Member of Parliament (MP) for Hindon in Wiltshire. It is debated whether a letter written to a current Member of Parliament from his father ensured him the position or if his father offered £2600. In 1802, after years of never addressing the House, he finally withdrew from a parliamentary career. His tastes lay wholly in the direction of literature, and his play The Castle Spectre (1796) enjoyed a long popularity on the stage. The Minister (a translation from Friedrich Schiller's Kabale und Liebe), Rolla (1797, a translation from August von Kotzebue), and numerous other operatic and tragic pieces, appeared in rapid succession. The Bravo of Venice, a translation of the German author Johann Heinrich Daniel Zschokke's Abaellino written in 1794, was published in 1804; after The Monk it is his best known work. The Bravo of Venice is considered “very chaste” in its translation by adhering strongly to the original, a fact which Lewis notes in the Preface.

The death of his father in 1812 left him with large fortune, and in 1815 he set off for the West Indies to visit his estates; in the course of this tour, which lasted four months, the Journal of a West India Proprietor, published posthumously in 1834, was written. A second visit to Jamaica was undertaken in 1817, in the hope of becoming more familiar with, and able to ameliorate, the condition of the slave population. However, the fatigues to which he exposed himself in the tropical climate brought on yellow fever which resulted in his death during the homeward voyage back to England. He was buried at sea. The exact dates of his death are debated, with some believing it to be 14 May and others, 16 May.

Lewis held two estates, Cornwall estate in Westmoreland and Hordley estate in St Thomas in the East. According to the slave registers, Hordley was co-owned with George Scott and Matthew Henry Scott and their shares were purchased by Lewis in 1817.

Lewis visited Percy Bysshe Shelley and Mary Shelley at Geneva, Switzerland, in the summer of 1816 and recounted five ghost stories which Shelley recorded in his "Journal at Geneva (including ghost stories) and on return to England, 1816", beginning with the entry for 18 August, which was published posthumously.

The Life and Correspondence of M.G. Lewis, in two volumes, was published in 1839. The Effusions of Sensibility, his first novel, was never completed.

As a writer, Lewis is typically classified as writing in the horror - gothic genre along with authors Charles Robert Maturin and Mary Shelley. Though he was most assuredly influenced by Ann Radcliffe’s The Mysteries of Udolpho and William Godwin’s Caleb Williams, taking Radcliffe’s obsession with the supernatural and Godwin’s narrative drive and interest in crime and punishment, Lewis differed with his literary approach. Whereas Radcliffe would allude to the imagined horrors under the genre of terror - gothic, Lewis defined himself by disclosing the details of the gruesome scenes, earning him the title of horror - gothic novelist. For Lewis, by giving the reader the information, he provides a more fulfilling experience. In the article “Matthew Lewis and the Gothic Horror of Obsessional Neurosis,” Ed Cameron argues that “Lewis disregards and often parodies the sentimentality found in Radcliffe’s work.” Without ambiguities, however, Lewis sometimes appears excessive in his materialized descriptions of the supernatural, losing a sense of wonder in the process.

Lewis is often criticized for a lack of originality. Though much of Lewis’ career dealt with the translation of other texts, these criticisms more often refer to his novel The Monk and his play The Castle Spectre. Beginning with The Monk, Lewis starts the novel with an advertisement which reads:

The first idea of this Romance was suggested by the story of the Santon Barsisa, related in The Guardian. – The Bleeding Nun is a tradition still credited in many parts of Germany; and I have been told, that the ruins of the Castle of Lauenstein, which She is supposed to haunt, may yet be seen upon the borders of Thuringia. – The Water - King, from the third to twelfth stanza, is the fragment of an original Danish Ballad — And Belerma and Durandarte is translated from some stanzas to be found in a collection of old Spanish poetry, which contains also the popular song of Gayferos and Melesindra, mentioned in Don Quixote. – I have now made a full avowal of all the plagiarisms of which I am aware myself; but I doubt not, many more may be found, of which I am at present totally unconscious.

While some critics, like those of The Monthly Review, saw combinations of previous works as a new invention, others, including Samuel Coleridge, have argued that by revealing where Lewis found inspiration, he surrendered part of his authorship. This bothered Lewis so much that in addition to a note written by Lewis in the fourth edition of The Monk, he also included notes to the text when he published The Castle Spectre as a way to counteract any plagiarist accusations. However, his success is debatable.