The story takes place during the late nineteenth century, the era the book was written. Horace Holly's account begins in Cambridge, England, where he lives a solitary life as a scholar. As the guardian of his dead friend's son, Leo Vincey, Holly accompanies the handsome young man on his quest to Africa to avenge the death of his ancient ancestor, an Egyptian priest named Kallikrates. Centuries ago Kallikrates had been killed by the goddess Ayesha when he rejected her love for that of another woman. On his twenty-fifth birthday, Leo Vincey learns that, because he is the sole descendant of the ancient family of Kallikrates, it is his duty to "seek out the woman [Ayesha, or She] and learn the secret of Life, and if thou mayest, find a way to slay her." Leo also learns that his own father had tried to carry out these ancient instructions...