She is the story of Cambridge professor Horace Holly and his ward Leo Vincey, and their journey to a lost kingdom in the African interior. The journey is triggered by a mysterious package left to Leo by his father, to be opened on his 25th birthday; the package contains an ancient shard of pottery and several documents, suggesting an ancient mystery about the Vincey family.

Holly and Leo eventually arrive in eastern Africa where they encounter a primitive race of natives and a mysterious white queen, Ayesha, who reigns as the all-powerful «She» or “She-who-must-be-obeyed”.