At the Royal Academy he became friendly with fellow student William Holman Hunt, and contributed with Hunt and Dante Gabriel Rossetti to the Cyclographic Society. In 1848 the three helped form the Pre-Raphaelite Brotherhood. His first Pre-Raphaelite painting was Isabella (1848-9, Walker Art Gallery, Liverpool), which he exhibited at the Royal Academy in 1849. His entry for the following year, Christ in the House of His Parents ('The Carpenter's Shop') (1849-50, Tate Gallery N03584), was received unfavourably.
In 1855 he married Effie Chalmers, Ruskin's former wife, with whom he had fallen in love while he was holidaying with the Ruskins in Scotland. The couple settled in Perth, where he painted Autumn Leaves (1855-6, City of Manchester Art Galleries).
Between 1855 and 1864 Millais made illustrations for numerous publications, including the Moxon edition of Tennyson's poems (1857), the magazine Once a Week (1859 onwards) and several novels by Trollope. He moved back to London in 1861, where he achieved popular success as a painter of child subjects such as Bubbles (1886, A. & F. Pears Ltd.), which became famous as an advertisement for Pears soap. Also popular were his paintings of beautiful young women, such as Stella (1868, Manchester City Art Gallery). He built up a practice as a portraitist from the early 1870s, his sitters including Thomas Carlyle (1877), Lillie Langtry (1878), Gladstone (1879 and 1885), Disraeli (1881) and Tennyson (1881).
Millais was made an Associate of the Royal Academy in 1853, and a full member in 1863. In 1885 he was created a baronet and in 1896 was elected President of the Royal Academy, but died shortly thereafter in London. He is buried in St Paul's Cathedral.
John Guille Millais, The Life and Letters of Sir John Everett Millais, 2 volumes, London 1899
Leslie Parris (ed.), The Pre-Raphaelites, exhibition catalogue, Tate Gallery, London 1984, reprinted 1994