Born in New York City, she wrote, under the name of "Elizabeth Wetherell", thirty novels, many of which went into multiple editions. However, her first novel,The Wide, Wide World (1850), was the most popular. It was translated into several other languages, including French, German, and Dutch. Other than Uncle Tom's Cabin, it was perhaps the most widely circulated story of American authorship. Other works include Queechy (1852), The Law and the Testimony, (1853), The Hills of the Shatemuc, (1856), The Old Helmet (1863), and Melbourne House (1864). In the nineteenth-century, critics admired the depictions of rural American life in her early novels. American reviewers also praised Warner's Christian and moral teachings, while London reviewers tended not to favor her didacticism. Early twentieth-century critics classified Warner's work as "sentimental" and thus lacking in literary value. In the later twentieth century, feminist critics rediscovered The Wide, Wide World, discussing it as a quintessential domestic novel and focusing on analyzing its portrayal of gender dynamics.

Some of her works were written jointly with her younger sister Anna Bartlett Warner, who sometimes wrote under the pseudonym "Amy Lothrop". The Warner sisters also wrote famous children's Christian songs. Susan wrote Jesus Bids us Shine while Anna was author of the first verse of the well-known children's song Jesus Loves Me, This I Know, which she wrote at Susan's request.

Both sisters became devout Christians in the late 1830s. After their conversion, they became confirmed members of the Mercer Street Presbyterian church, although in later life, Warner became drawn into Methodist circles. The sisters also held Bible studies for the West Point cadets. When they were on military duty, the cadets would sing "Jesus loves me." The popularity of the song was so great that upon Warner's death, she was buried in the West Point Cemetery.

Warner could trace her lineage back to the Puritan Pilgrims on both sides. Her father was Henry Warner, a New York City lawyer originally from New England, and their mother was Anna Bartlett, from a wealthy, fashionable family in New York's Hudson Square. When Warner was a young child, her mother died, and her father's sister Fanny came to live with the Warners. Although Henry Warner had been a successful lawyer, he lost most of his fortune in the Panic of 1837 and in subsequent lawsuits and poor investments. The family had to leave their mansion at St. Mark's Place in New York and move to an old Revolutionary War-era farmhouse on Constitution Island, near West Point, NY. In 1849, seeing little change in their family's financial situation, Susan and Anna started writing to earn money.

Susan Warner died in Highland Falls, New York.