Hughes was born in London. In 1846 he entered the art school at Somerset House, his first master being Alfred Stevens, and later entered the Royal Academy schools. Here he met John Everett Millais and Holman Hunt, and became one of the Pre-Raphaelite group of painters. His first picture, Musidora, was hung at the Royal Academy when he was only 17, and thenceforth he contributed almost annually not only to the Royal Academy but later also to the Grosvenor and New Gallery exhibitions.
In 1855 Hughes married Tryphena Foord, his model for April Love. Hughes died in Kew Green, London in 1915, leaving about 700 known paintings and drawings, along with over 750 book illustrations. Following the death of Tryphena Hughes in 1921, their daughter Emily had to move to a smaller house. There was, therefore, a shortage of space. As a result, she had her father’s remaining preparatory sketches, and all his private papers and correspondence, destroyed. He was the father of the English painter Arthur Foord Hughes and the uncle of another, Edward Robert Hughes.
Hughes is buried in Richmond Cemetery.