Season 1's plot was adapted from the first novel in Jeff Lindsay's "Dexter" series, Darkly Dreaming Dexter. Subsequent seasons have featured original storylines.
Orphaned at the age of three and harboring a traumatic secret, Dexter (Michael C. Hall, Six Feet Under) was adopted by a Miami police officer named Harry Morgan (James Remar), who recognized Dexter's sociopathic tendencies and taught him to channel his gruesome passion for thrill killing by giving it a constructive direction: killing people who deserve it. Most have slipped through the justice system, due to loopholes and technicalities in the law or were never apprehended.
To hide in plain sight and to erase his own crimes, Dexter works as a blood spatter analyst for the Miami Metro Police Department. Although his drive to kill is unflinching (otherwise overcome by a feeling of "emptiness") Dexter is, through extensive instruction from Harry, able to fake normal emotions and keep up his appearance as a socially-responsible human being. Flashbacks throughout the series show how Harry (dead of natural causes several years before the start of Season One, but later determined overdosed due to not being able to deal with Dexter's killings) instructed Dexter on the art of appearing normal, and he follows Harry's instructions as a sacred "Code of Harry." In accordance with this code, most of Dexter's victims must be killers themselves; people who have killed multiple times with no remorse. Dexter must also have proof that the criminals are definitely guilty before he takes action. In the episode "Return to Sender", Dexter is shown to have used the alias "Patrick Bateman" to procure powerful sedatives to use on victims. This is the same name used by Bret Easton Ellis for the serial killer in his 1991 novel American Psycho (as well as the 2000 film of the same name), who, like Dexter, is a seemingly normal person by day but a ruthless serial killer by night.
Dexter has a girlfriend, Rita Bennett (Julie Benz), whom he dates in order to appear normal. Rita is psychologically damaged from past rape and abuse by her former husband (a violent felon and drug addict) and is too distraught to want to be in an intimate relationship. This suits Dexter, who believes he is unable to fake intimate emotions. Dexter hopes to keep up his facade of normality by distancing himself from Rita. At the same time, he feels genuine affection for Rita and her two children, Astor and Cody.
The first season focuses mostly on "The Ice Truck Killer" — a serial killer eluding the Miami PD who is communicating with Dexter through his crime scenes. Dexter's adoptive sister (and Harry's biological daughter) Debra (Jennifer Carpenter) begins dating Rudy, who is revealed to the audience to be the Ice Truck Killer. At the end of the season, Rudy reveals that he is really Dexter's biological brother, Brian Moser, and describes additional details of Dexter's early childhood, complementing Dexter's vague memories as well as details he has been piecing together over the length of the season. The formative event for the brothers was witnessing their mother and several other people being chainsaw-butchered by a drug dealer and being locked in a cargo container for two days with the dismembered corpses, the floor covered in blood. Dexter (then three years old) was adopted by Harry, who was the first police officer to enter the cargo container, while Brian (several years older) was more obviously traumatized and spent much of his childhood institutionalized. Harry deliberately hid the details about the crime from Dexter, as well as information about his biological family. Dexter's perception of Harry's betrayal begins to weigh on him.
Rudy/Brian kidnapped Debra, having intended all along that he and Dexter would kill her together to cement their bond and sever the ties between Dexter and his adoptive family. Dexter instead turns against Brian and ultimately kills him, making the death look like a suicide. Everyone, including Debra, remains unaware of the exact connection between Dexter and Rudy/Brian and a recurring theme throughout the series is her jealousy of the perceived preferential treatment Harry gave Dexter. She is unaware of Harry's training or Dexter's tendencies. Dexter feels some regret over killing Brian, the one person who fully understood him, in order to save Debra, whom he knows would turn away from him if she ever learned his true nature.
Dexter uses his calculated charm to become well-liked by all of his colleagues, with the exception of Sgt. James Doakes (Erik King), who finds him odd (often calling him a "freak" or a "creep") and openly accuses him of being up to something, as well as harboring vague suspicions that Dexter has some connection to the Ice Truck Killer and even keeping Dexter under some surveillance. The tension between the two is an ongoing plot motif.
Dexter sets up Rita's ex-husband to look like he violated his parole. While back in prison proclaiming his innocence, he points Rita to a clue to the truth about Dexter. The season ends with Dexter and his sister entering a crime scene, with Dexter imagining a ticker tape parade for himself, complete with confetti and airplane fly-over, and the crowd praising him for his fine work "taking out the garbage" (i.e. killing those who prey on the weak and vulnerable).