Maclise was born in Cork, Ireland, the son of Alexander McLish (also known as McLeish, McLish, McClisse or McLise), a tanner or shoemaker, but formerly a Scottish Highlander soldier. His education was of the plainest kind, but he was eager for culture, fond of reading, and anxious to become an artist. His father, however, placed him in employment, in 1820, in Newenham's Bank, where he remained for two years, before leaving to study at the Cork School of Art. In 1825 it happened that Sir Walter Scott was travelling in Ireland, and young Maclise, having seen him in a bookseller's shop, made a surreptitious sketch of the great man, which he afterwards lithographed. It became very popular, and led to many commissions for portraits, which he executed, in pencil.
Various influential friends recognised Maclise's genius and promise, and were anxious to furnish him with the means of studying in London; but refusing all financial assistance, he saved the money himself and arrived in the capital on 18 July 1827. There he made a sketch of Charles John Kean, the actor, which, like his portrait of Scott, was lithographed and published, making the artist a considerable sum. He entered the Royal Academy schools in 1828, eventually being awarded the highest prizes open to students.
Maclise exhibited for the first time at the Royal Academy in 1829. Gradually he began to confine himself more exclusively to subject and historical pictures, varied occasionally by portraits – such as those of Lord Campbell, novelist Letitia Landon, Dickens, and other of his literary friends. In 1833, he exhibited two pictures which greatly increased his reputation, and in 1835 the Chivalric Vow of the Ladies and the Peacock procured his election as associate of the Academy, of which he became full member in 1840. The years that followed were occupied with a long series of figure pictures, deriving their subjects from history and tradition and from the works of Shakespeare, Goldsmith and Le Sage.
He also designed illustrations for several of Dickens's Christmas books and other works. Between the years 1830 and 1836 he contributed to Fraser's Magazine, under the pseudonym of Alfred Croquis, a remarkable series of portraits of the literary and other celebrities of the time – character studies, etched or lithographed in outline, and touched more or less with the emphasis of the caricaturist, which were afterwards published as the Maclise Portrait Gallery (1871). During the rebuilding of the Houses of Parliament in London in 1834–1850 by Charles Barry, Maclise was commissioned in 1846 to paint murals in the House of Lords on such subjects as Justice and Chivalry.
In 1858, Maclise commenced one of the two great monumental works of his life, The Meeting of Wellington and Blücher, on the walls of Westminster Palace. It was begun in fresco, a process which proved unmanageable. The artist wished to resign the task, but, encouraged by Prince Albert, he studied in Berlin the new method of water-glass painting, and carried out the subject and its companion, The Death of Nelson, in that medium, completing the latter painting in 1864.
Maclise's vast painting of The Marriage of Strongbow and Aoife (1854) hangs in the National Gallery of Ireland, Dublin. It portrays the marriage of the main Norman conqueror of Ireland "Strongbow" to the daughter of his Gaelic ally. By the grand staircase of Halifax Town Hall, which was completed in 1863, there is a wall painting by Maclise.
The intense application which he gave to these great historic works, and various circumstances connected with the commission, had a serious effect on the artist's health. He began to shun the company in which he formerly delighted, his old buoyancy of spirits was gone, and when, in 1865, the presidency of the Royal Academy was offered to him he declined the honour. He died of acute pneumonia on 25 April 1870 at his home 4 Cheyne Walk, Chelsea.
His works are distinguished by powerful intellectual and imaginative qualities, but, in the opinion of Monkhouse, a late Victorian critic, somewhat marred by harsh and dull colouring, by metallic hardness of surface and texture, and by frequent touches of the theatrical in the action and attitudes of the figures. His fame rests most securely on his two greatest works at Westminster.
A memoir of Maclise, by his friend William Justin O'Driscoll, was published in 1871.
The works of Maclise in portraiture were celebrated in 1972 at an exhibition in the National Portrait Gallery.
The Crawford Gallery in Cork, Ireland, Maclise's native town, held a major exhibition of his works from October 2008, opened by David Puttnam.
The preliminary sketch for The Meeting of Wellington and Blücher was displayed at the Royal Academy of Arts from 2 September 2015 to 3 January 2016, to commemorate the 200th anniversary of the Battle of Waterloo. It had been displayed previously from 23 May until 23 August at the Royal Armouries in Leeds as part of the Waterloo 1815: The Art of Battle exhibition.