Louis de Pointe du Lac lives in 1910 New Orleans as executor-in-charge of his family's fortune; when he meets the vampire Lestat, Louis' life begins to unravel in otherworldly ways; in 2020, Louis tells his story to journalist Daniel Molloy.

Beginning his life as a vampire, Louis learns the rules of vampirism from his maker and companion Lestat; Louis discovers increasing differences between himself and Lestat; in Dubai, Louis reveals more of his modern-day vampire lifestyle to Molloy.

Louis continues his life as a businessman of Storyville. When an old friend comes to town, Louis's relationship with Lestat is tested. Louis' business intertwines with growing tensions in New Orleans, leading to a new chapter in Louis' vampire life.

Claudia's transformation into a vampire teen completely changes Louis and Lestat's lives. As Claudia asks more questions, Louis and Lestat are forced to confront questions about making a teen vampire. Claudia learns dark realities of her new life.

Claudia leaves home for a college sojourn and to learn more about vampires. Meanwhile, Louis and Lestat live through the Depression and received surprising news from Louis' sister. When Claudia returns, tensions in the family come to a boiling point.

Lestat attempts to make amends with Louis. The vampire family decides to live together once more. A surprising action from Lestat leads the family to decide to leave New Orleans, once and for all. In Dubai, Molloy has a shocking realization.