In 1892 his father married Isabel Warner. Although he got on fairly well with his step-mother, at the age of thirteen he ran away from home, wanting to become a drummer boy in the Spanish-American War.
He was educated at Oberlin Academy and Yale University. In 1906 Upton Sinclair, a member of the Socialist Party, and a successful writer, decided to use some of his royalties into establishing, Helicon Home Colony, a socialist community at Eaglewood. One of those who joined was Sinclair Lewis, who was to be greatly influenced by Upton Sinclair's views on politics and literature. Four months after it opened, a fire entirely destroyed Helicon. Later, Sinclair blamed his political opponents for the fire.
After his graduation from Yale University, Lewis worked for newspapers and publishing houses. His main objective was to be a full-time writer. For a period he was a member of Carmel, California writers' colony. He met Jack London and sold him plots of novels, including the one he used for The Assassination Bureau.
In 1908 Lewis moved to New York City where he became a freelance writer. His first novel, Hike and the Aeroplane was published in 1912. He married Grace Livingston Hegger in 1914. They had one son, Wells Lewis (1917–1944), who was named after author H.G. Wells.
Sinclair Lewis published Our Mr Wrenn: The Romantic Adventures of a Gentle Man in 1914. This was followed by The Trail of the Hawk (1915), but it was his novel Main Street (1920), that established his reputation as a great novelist. The book sold 180,000 copies in the first six months, and within a few years sales were estimated at two million.
Lewis's greatest work, Babbitt, was published in 1922. One critic wrote "The creation of George F. Babbit - whose name has become synonymous with bourgeois mediocrity - an intellectually empty, emotionally immature man of dubious morals who nevertheless remains a lovable comicstrip figure, is Lewis's greatest accomplishment."
His next novel, Arrowsmith (1925), about a young doctor's attempt to maintain his integrity in a world of commercialism, was awarded a Pulitzer Prize. His next novel, Elmer Gantry, the story of a revivalist minister, appeared in 1927. Dodsworth (1929), was an account of a retired automobile manufacturer travelling in Europe. Both books were well-received and in 1930 Lewis became the first American novelist to be awarded the Nobel Prize for Literature. When he received the prize he warned that writers were "still afraid of any literature which is not a glorification of everything American, a glorification of our faults as well as our virtues."
Although no longer an active socialist, Lewis continued to write books that revealed his commitment to political and social change. This included Ann Vickers (1933), a book about the women's movement and prison reform, and It Can't Happen Here (1935) a warning about the dangers of fascism.
Sinclair Lewis was an alcoholic and after a heart attack his doctors advised him that he must stop drinking if he wanted to live. Lewis was unable to do this and died of paralysis of the heart in Rome on 10th January 1951.