Based on a true story, The Book of Negroes tells the story of Aminata, a young girl abducted from her village in Mali aged 11 in 1755. Following a deathly journey on a slave ship where she witnesses the brutal repression of a slave revolt, Aminata is sold to a plantation owner in South Carolina, who rapes her. She is brought to New York, where she escapes her owner, and finds herself helping the British by recording all the freed slaves on the British side in the Revolutionary War in The Book of Negroes (a real historical document that can be found today at the National Archives at Kew).

Aminata is sent to Nova Scotia to start a new life, but finds more hostility, oppression, and tragedy. Separated from her one true love, and suffering the unimaginable loss of both her children who are taken away from her, she eventually joins a group of freed slaves on a harrowing odyssey back to Africa, and ends up in London as a living icon for Wilberforce and the other Abolitionists.