Sir John Murray was born on December 18, 1851, in London, England, the eldest son of John Murray (1808–1892) who was the third of his name to be head in a succession of the publishing house founded in 1768 by John Murray the first, who was followed by John Murray the second (1778–1843). Publishing, therefore, was to him a hereditary profession, and in due course, he became John Murray the Fourth.

He was educated at Eton and Magdalen College, Oxford, and then entered the firm's house in Albemarle Street, passing through all its departments until, in 1892, he succeeded his father as its head. In 1917, Murray's house acquired the publishing business of Smith, Elder & Co., and this enabled him, late in life, to take a personal interest in many of the younger school of novelists. From 1922 until he died in 1928, he edited the Quarterly Review and surveyed politics from an interested and yet detached point of view. In Byron, Murray took a hereditary interest, editing his Correspondence in 1922; and it was in honour of the Byron centenary in 1924 that he received the D.Ph. degree from the University of Athens and was created a commander of the order of the Redeemer (of Greece). In recognition of his publication of the first and second series of volumes of the Letters of Queen Victoria, he was created C.V.O. in 1912 and K.C.V.O. in 1926. He found time not only to edit Gibbon's Autobiography (1897) and to write John Murray III: a Memoir (1919), but to be chairman of the Publishers' Association from 1898 to 1899. He also acted as Justice of Peace in London and was a member of the board of the Hospital for Sick Children and its vice-president.

In 1878, he married Katherine Evelyn Leslie (1858–1938). He died on November 30, 1928, in Hove, Sussex, England.