The Vampire Lestat is a story of wicked but beautiful beings, good and evil, the quest for knowledge and, ultimately, love. The vampire Lestat recounts his mortal and immortal history as he creates emotional turmoil in his wake. The story also follows as he seeks answers and meanings of the origin of his immortality. The lush imagery abounds from his early days as the marquis' son in the Auvergne, to Paris as the indefatigable Lelio on stage, to his fledgling days as a vampire, to his quest for knowledge from the ancient vampire Marius, and back to Lestat's wild on stage performance in San Francisco.

From the beginning, Lestat, even as a mortal, is seen as impetuous and stubborn. He consistently goes against the natural grain of things. There is not any one thing that occurs to him that he cannot or should not do. As a young man, he hunts a pack of wolves and is victorious. This one event is the catalyst for much of the action that comes after. His life is permanently changed with his relationship with his family. Ultimately, he takes off with his friend Nicholas to the city of Paris to be a big success on the stage.

It is while they are in Paris that things take a different path for Lestat. One night, while on stage, he has his first encounter with a vampire. This vampire, Magnus, later breaks into Lestat's apartment and takes him away to his lair and makes him a vampire. Shortly after, Magnus goes into the fire and kills himself, leaving Lestat on his own to figure things out. When Lestat then gets word that his dying mother is in Paris to see him, he goes to her and reveals his true nature. With her consent, he makes her a vampire as well and saves her from her own death.

While the two of them roam Paris and learn how to use their abilities, they come across a coven of vampires that live beneath les Innocents cemetery. These vampires live by old rules put in place long ago. At Lestat's urging, they abandon the old ways and inhabit a theatre and begin to put on nightly performances. When Lestat makes his friend Nicholas a vampire, he leaves Nicholas with this coven of vampires, headed up by their leader, Armand.

Lestat and Gabrielle travel through various countries until Gabrielle leaves him for the jungles of Africa. Lestat seeks out an ancient vampire, Marius, and visits with him on his Greek island. It is there that he sees Those Who Must Be Kept, who embody the origin of their species. When Lestat disrupts their repose by playing the violin, Marius makes Lestat go. From there, he goes to the New World and settles in New Orleans. Eventually he goes into the earth and slumbers until the year 1984.

When he awakens, he joins a rock band and they become The Vampire Lestat. They are a huge hit. At the end of Lestat's story, the band is scheduled to perform in San Francisco and both Louis and Gabrielle come out to be with him. As they whisk him away from the boisterous throngs after the show, the other vampires that are out to kill Lestat explode into flames. When Lestat goes into the ground for his daytime slumber he knows he is not alone. After several thousand years of silence, the queen of the vampires, Akasha, has awakened and come to him.