Up from Slavery is set in the American South (specifically Virginia, West Virginia, and Alabama) between 1856 and 1900. As an autobiography, the book follows Washington as he moves from Franklin County, Virginia (where he and his mother were enslaved), to West Virginia (where he and his mother lived with Washington’s stepfather after emancipation), then back to Virginia (where Washington attended the Hampton Institute), and finally to Tuskegee, Alabama (where he helped found and run the Tuskegee Institute).
The first chapter of the book describes the conditions of Washington’s life as a slave from when he was born until he was nine years old, leading up to the end of the Civil War in 1865. After the Union defeated the Confederacy and Lincoln officially emancipated all enslaved people in the United States, Washington began his life as a free man.
The next portion of Washington’s autobiography covers the Reconstruction period of American history, when the country was trying to rebuild after the Civil War and Black Americans were swiftly granted legal rights formerly stripped from them, such as the right to vote, run for office, start businesses, and own property. While federal military occupation in the South meant that these new legal protections were initially enforced during President Johnson's tenure, Presidents Grant and Hayes eventually removed the troops. As a result, Black Americans began to face violence and discrimination in the South once again. In Washington’s opinion, the Reconstruction Era led to too much freedom and empowerment for Black Americans too quickly—he believed in political uplift for his community, but thought it should be more gradual (so as to ensure Black Americans were prepared for new responsibilities, as well as to avoid backlash from angry white Americans).
Near the end of the book, the setting changes as Washington spends three months traveling through Europe as part of an all-expenses-paid trip. He is impressed with certain aspects of European society, such as farming practices in Holland and a more organized and relaxed culture in England.