Red Dragon by Thomas Harris is the prequel to the novel that spawned the popular movie, Silence of the Lambs, and is the first appearance of the famed character, "Hannibal Lecter." The plot revolves around the man who captured Hannibal Lecter three years before in his pursuit for another insane serial killer. Red Dragon is a crime novel full of suspense and forensic technology that still stands with the best of its genre more than twenty years after it was written.

Will Graham is a retired FBI forensics expert. Graham lives in Florida with his new wife and step son, content to be out of the world of evil. However, his old colleague and friend, Jack Crawford has come to him to ask for his help. Another psychopathic killer is on the loose, and Crawford knows only someone with Graham's unique gifts can help them catch him.

Graham jumps right into the case by visiting the home of the latest killers, submerging himself in the crimes to get a feel for the family, and for the man who murdered them. By submerging himself so completely, however, Graham places himself in a fragile mental state that has him constantly at war with himself and his ability to relate so easily to these types of killers.

The clues are thin at first. There are teeth impressions and broken mirrors that tell Graham a few things about the killer's personality. However, there is nothing solid to go on even after they find an eyewitness who saw a stranger watching the victim's home days before the murders. It is not until later, until after he visits the home of the second family, that Graham realizes the killer likes to watch the family for hours before he strikes. Graham finds a tree in which the killer sat and watched the children bury a family pet. This opens a door for Graham. If only he could find a connection between the two families.

While Graham searches for the killer, the reader is introduced to Francis Dolarhyde. Dolarhyde is a shy film processor who grew up with a devastating deformation, cleft palate. Dolarhyde was abused by his grandmother, abandoned by his mother, and has now become obsessed by a painting of William Blake's The Great Red Dragon and the Woman Clothed with the Sun. Dolarhyde believes that by committing horrific crimes, he is becoming the Great Red Dragon.

After learning that the killer has Graham's address thanks to Hannibal Lecter, Graham agrees to work with a tabloid reporter he despises to lure the killer into a trap. Graham, an FBI psychologist, and Crawford devise a group of lies that they feel will anger the killer and encourage him to come after Graham. However, instead of going after Graham, the killer goes after the reporter and kills him.

During this time, Dolarhyde has met a blind woman, named Reba, and fallen in love. This feeling causes a split in his personality. Dolarhyde can now hear the Dragon talking to him. The Dragon wants Dolarhyde's girlfriend killed. To prevent this, Dolarhyde goes to the Brooklyn Museum and arranges to see the original Blake painting. During this visit, Dolarhyde eats the painting in order to become one with the Dragon, once more.

While Dolarhyde is in Brooklyn, Graham receives some home movies of the Jacobi family that had gone missing after their deaths. Graham watches the movies, as well as the movie of the Leeds family, the second family murdered. He realizes the killer must have seen these movies in order to know everything he did about the families. Graham then finds the connection he has been searching for. Both sets of film were processed at the same company.

When Dolarhyde returns to St. Louis, he goes straight to his work place to find his girlfriend. Instead he finds Graham there searching through personnel files. Dolarhyde sneaks out and devises a plan with the Dragon to get away. Dolarhyde kills a man Reba had been dating and takes Reba. Back at his home, Dolarhyde kills himself and sets his house on fire. Reba is barely able to escape.

Graham, satisfied that Dolarhyde is dead, goes home with his family. However, a few days after they return, Dolarhyde appears and tries to kill him. Molly manages to get Dolarhyde away from Graham and leads him up to the house. Then, Molly shoots Dolarhyde and kills him. In the hospital, Crawford fills Graham in on how Dolarhyde managed to fake his death by using another person's body as a decoy. Graham, after all is said and done, finally comes to terms with his own mental stability and the capacity to commit such horrific crimes in his fellow human beings.