Incidents in the Life of a Slave Girl carries the reader through the events of one woman's birth into slavery, her sufferings under that institution, and the manner in which she is eventually able to free herself and her family from bondage and create a new life in the North.

Through the pseudonym Linda Brent, the author, Harriet Jacobs, begins her story by telling us about her unusually (for a slave) happy childhood, which comes to an abrupt end as the deaths of her mother, father and a kind first mistress leave her an orphan and the helpless property of Dr. Flint.

Linda manages to adjust to life with the Flints, largely due to her maternal grandmother, who has been freed from slavery and offers whatever support she can to her orphaned slave grandchildren. However, as Linda approaches maturity, she becomes the object of her master's lecherous advances. She makes every effort to rebuff his advances, but since she is his legal property, this becomes very difficult. She ultimately decides that the only way to avoid her master's sexual advances is to become the mistress of another prominent gentleman in the town. She bears this gentleman two children.

Now, as the mother of two, Linda is not only still frustrated by her lack of power to control her own destiny, but also by her inability to protect the best interests of her children. When she becomes aware that her master intends to take her children to the plantation to break them in for a life of backbreaking labor, she plans her escape.

After escaping from slavery, Linda spends many years uncomfortably hidden in her grandmother's home. During this time she effectively secures the freedom of her children and eventually is able to escape to the North herself. Even after she reaches the North, she is still in danger. The passage of the Fugitive Slave Law makes it possible for her to be caught and returned to the South as Dr. Flint's rightful property at any time. She is reunited with her children in the North, however, and is able to gain employment to provide for them and educate them. While she has successfully secured her own freedom and that of her children at the end of the narrative, she still has not achieved her goal of obtaining a home of her own where she and her children can live together.

Interspersed throughout the story of her own life, Linda shares with the reader the experiences of her family, friends, and others in slavery. Through these anecdotes, the reader learns about a wide range of different slave experiences and about those who are indirectly affected by this institution.