Interview with the Vampire is a story of immortality, loyalty, and detachment. The main plot surrounds three individuals brought and held together by the bond of immortality. The story begins with the vampire, Louis, who meets with a boy conducting an interview of his life. The journey begins with tragedy in a young mortal's life that brings him to an encounter with a vampire that changes him forever. Eternally in search of answers as to their true nature and origins, Louis faces the death of his humanity, the betrayal of other vampires, and the death of a companion dear to him. In the end, Louis understands that the road of immortality is best traveled alone.

Before Louis' story begins, he meets a young boy who conducts interviews. They meet in a room in San Francisco, which is where the action begins. Louis tells his story which begins in a time to when he was a mortal man in late eighteenth century New Orleans. After tragedy strikes his family, he encounters the vampire Lestat who makes him one of the undead. Almost immediately, Louis grapples with his new, evil nature and his lost humanity. Unable to slay mortals in the beginning, he exists off of the blood of animals until he comes upon a young girl, five years of age. He and Lestat take the girl and make her a child vampire. Together they live almost happily for seventy years, until Claudia begins to ask questions about her origins.

Cursed to live for eternity in a child's body, Claudia is furious that she will never physically grow into adult. She makes the decision to rise up against Lestat, whom she blames for her nature. She lashes out against him, and both she and Louis believe him dead when they prepare to leave for Europe. Once overseas, they encounter nothing but mindless living corpses until they arrive in Paris. It is in Paris that they meet other vampires such as themselves. Claudia, however, realizes that she is in danger from these beings and begs Louis to make another vampire, Madeline, who will care for and protect Claudia. It is not long after he agrees to this that the Paris vampires kill Claudia for her crime against Lestat.

Louis gets his revenge by torching the theatre where they live and kills anyone that attempts escape. He discovers soon after that Armand is alive and together they travel the world before coming back to New Orleans. Once there, Louis finds Lestat living a solitary existence, afraid of the modern world. Louis refuses to go back to him and walks away. Armand eventually leaves him and he carries on his eternal existence, completely alone, which is how he prefers it.