See also: List of The Vampire Diaries episodes

The series follows the life of Elena Gilbert (Nina Dobrev), who falls for a century-old vampire named Stefan Salvatore (Paul Wesley). Their lives grow more and more complicated as Stefan's vicious and malevolent elder brother Damon (Ian Somerhalder) returns to the town of Mystic Falls with a plan to wreak havoc on the town and also to plan a vendetta against his younger brother. Both brothers begin to show affection towards Elena, mainly because of her resemblance to their past love Katherine. It is revealed that Elena is Katherine's doppleganger, who eventually returns with plans against the trio.

The series is set in the fictional town of Mystic Falls, Virginia, a town charged with supernatural history. Other story lines revolve around the other inhabitants of the town, most notably Elena's younger brother Jeremy (Steven R. McQueen), Elena's best friend Bonnie (Katerina Graham), Elena's close friend, Caroline (Candice Accola) and Elena's childhood friend and ex-boyfriend, Matt (Zach Roerig). The town's politics are orchestrated by descendants of the original founding families, all comprising a "Founders' Council". Some of the founding families of Mystic Falls include the Salvatores, the Gilberts, the Fells, the Forbes and the Lockwoods. They guard the town mainly from vampires, but also creatures such as werewolves and witches, some of whom are themselves members of the Founders' Council.