He was born in Sullivan, Indiana. From 1889-1890, he attended Indiana University at Bloomington before flunking out. Within a couple of years, he was writing for the Chicago Globe and then the St. Louis Globe-Democrat. In 1892 he married Sara White. Although they separated in 1909, they were never formally divorced.
His first novel, Sister Carrie (1900), told the story of a woman who fled her country life for the city (Chicago) and fell into a wayward life of sin. The publisher did little to promote the book, and it sold poorly. Dreiser took a job editing women's magazines until he was forced to resign in 1910 because of an inter-office romance. His second novel, Jennie Gerhardt was published the following year. Many of Dreiser's subsequent novels dealt with social inequality.
His first commercial success was An American Tragedy (1925), which was made into a film in 1931 and again in 1951.
Other works include the Trilogy of Desire about Frank Cowperwood, a fictionalized version of Charles Yerkes: The Financier (1912), The Titan (1914), and The Stoic (completed posthumously in 1947).
In 2001, two of his books, Sister Carrie and An American Tragedy, were named to the list of the 100 best English-language novels of the 20th century by the editorial board of the American Modern Library.