Written to his grandchildren, The Story of Mankind intermingles personal anecdotes with the history of Western civilization, covering the development of writing, art, and architecture, the rise of major religions, and the formation of modern (for 1921) nation states. Van Loon explains in the book how he selected what and what not to include by subjecting all materials to the question: Did the person or event in question perform an act without which the entire history of civilization would have been different?
After its first edition, Van Loon had another edition published later in the 1920s which included an extra essay, called "After Seven Years" about the effects of World War I. Since van Loon's death in 1944, The Story of Mankind has been added to extensively by his son, Gerrit van Loon. A current release covers events up to the mid-1980s.