Born in Martins Ferry, Ohio, originally Martinsville, to William Cooper and Mary Dean Howells, Howells was the second of eight children. His father was a newspaper editor and printer, and moved frequently around Ohio. Howells began to help his father with typesetting and printing work at an early age. During 1852, his father arranged to have one of Howells' poems published in the Ohio State Journal without telling him.

During 1856, Howells was elected as a Clerk in the State House of Representatives. During 1858, he began to work at the Ohio State Journal where he wrote poetry, short stories, and also translated pieces from French, Spanish, and German. He avidly studied German and other languages and was greatly interested in Heinrich Heine. During 1860, he visited Boston and met with American writers James Thomas Fields, James Russell Lowell, Oliver Wendell Holmes, Nathaniel Hawthorne, Henry David Thoreau, and Ralph Waldo Emerson.

Said to be rewarded for a biography of Abraham Lincoln used during the election of 1860, he gained a consulship in Venice. On Christmas Eve 1862, he married Elinor Mead at the American embassy in Paris. Among their children was the future architect John Mead Howells. Upon returning to the U.S., Howells wrote for various magazines, including Atlantic Monthly and Harper's Magazine. From 1866, he became an assistant editor for the Atlantic Monthly and was made editor in 1871, remaining in the position until 1881. During 1869, he first met Mark Twain, which began a longtime friendship. Even more important for the development of his literary style ... his advocacy of Realism ... was his relationship with the journalist Jonathan Baxter Harrison, who during the 1870s wrote a series of articles for the Atlantic Monthly on the lives of ordinary Americans (Fryckstedt 1958). He gave a series of 12 lectures on "Italian Poets of Our Century" for the Lowell Institute for their 1870-71 season.

He wrote his first novel, Their Wedding Journey, in 1872, but his literary reputation took off with the realist novel A Modern Instance, published in 1882, which described the decay of a marriage. His 1885 novel The Rise of Silas Lapham is perhaps his best known, describing the rise and fall of an American entrepreneur of the paint business. His social views were also strongly represented in the novels Annie Kilburn (1888) and A Hazard of New Fortunes (1890). He was particularly outraged by the trials resulting from the Haymarket Riot.

His poems were collected during 1873 and 1886, and a volume under the title Stops of Various Quills were published during 1895. He was the initiator of the school of American realists who derived through the Russians from Balzac and had little sympathy with any other type of fiction, although he encouraged new writers in whom he discovered new ideas.

During 1904, he was one of the first seven people chosen for membership in the American Academy of Arts and Letters, of which he became president.

Howells died in Manhattan on May 11, 1920. He was buried in Cambridge Cemetery in Massachusetts.

During 1928, eight years after Howells' death, his daughter published his correspondence as a biography of his literary years.

Howells also wrote plays, criticism, and essays about contemporary literary figures such as Henrik Ibsen, Émile Zola, Giovanni Verga, Benito Pérez Galdós, and, especially, Leo Tolstoy, which helped establish their reputations in the United States. He also wrote critically in support of American writers Hamlin Garland, Stephen Crane, Emily Dickinson, Mary E. Wilkins Freeman, Paul Laurence Dunbar, Sarah Orne Jewett, Charles W. Chesnutt, Abraham Cahan, and Frank Norris. It is perhaps in this role that he had his greatest influence. In his "Editor's Study" column at the Atlantic Monthly and, later, at Harper's, he formulated and disseminated his theories of "realism" in literature.

In defense of the real, as opposed to the ideal, Howells wrote,"I hope the time is coming when not only the artist, but thecommon, average man, who always 'has the standard of the arts in hispower,' will have also the courage to apply it, and will reject the idealgrasshopper wherever he finds it, in science, in literature, in art,because it is not 'simple, natural, and honest,' because it is not like areal grasshopper. But I will own that I think the time is yet far off,and that the people who have been brought up on the ideal grasshopper,the heroic grasshopper, the impassioned grasshopper, the self-devoted,adventureful, good old romantic card-board grasshopper, must die outbefore the simple, honest, and natural grasshopper can have a fair field."

• Venetian Life (1867)
• Italian Journeys (1867)
• Their Wedding Journey (1872)
• A Counterfeit Presentment (1877)
• The Lady of the Aroostook (1879)

The following were written during his residence in England and in Italy, as was The Rise of Silas Lapham in 1885.

• The Undiscovered Country (1880)
• A Fearful Responsibility (1881)
• Dr. Breen's Practice (1881)
• A Modern Instance (1882)
• A Woman's Reason (1883)
• Three Villages (1884)
• Tuscan Cities (1885)
• The Rise of Silas Lapham (1885)

He returned to the United States in 1886. He wrote various types of works, including fictional, poetry, and farces, of which The Sleeping-Car, The Mouse-Trap, The Elevator, Christmas Every Day, and Out of the Question are characteristic.

• Indian Summer (1886)
• The Minister's Charge (1886)
• Annie Kilburn (1887/88)
• Modern Italian Poets (1887)
• April Hopes (1888)
• A Hazard of New Fortunes (1890)
• Criticism and Fiction (1891)
• Christmas Every Day (1892)
• The World of Chance (1893)
• Jana Wilcox, or the Walls of the Labyrinth (1893)
• The Coast of Bohemia (1893)
• My Year In a Log Cabin (1893)
• A Traveler from Altruria (1894)
• Stops of Various Quills (1895)
• The Story of a Play (1898)
• Ragged Lady (1899)
• Their Silver Wedding Anniversary (1899)
• The Flight of Pony Baker (1902)
• The Kentons (1902)
• Questionable Shapes (1903)
• Son of Royal Langbrith (1904)
• London Films (1905)
• Certain Delightful English Towns (1906)
• Between the Dark and the Daylight (1907)
• Through the Eye of the Needle (1907)
• Heroines of Fiction (1908)
• The Landlord At Lion's Head (1908)
• My Mark Twain: Reminiscences (1910)
• New Leaf Mills (1913)
• Seen and Unseen at Stratford-on-Avon: A Fantasy (1914)
• The Leatherwood God (1916)
• Years of My Youth (autobiography) (1916)