Her first volume of verse, Forest Leaves, was published in 1845, and went through 20 volumes. In 1850, she started working in Columbus, Ohio as a schoolteacher. Three years later in 1853, she joined the American Anti-Slavery Society and became a travelling lecturer for the group.
In 1892, she published a novel about a rescued black slave and the Reconstructed South, called Iola Leroy, which was the first book published by an African-American. Later, she also wrote Minnie's Sacrifice, Sowing and Reaping and Trial and Triumph.
In addition, Harper was a member of the American Woman Suffrage Association.