The story is told in epistolary format, as a series of letters, diary entries, and ships' log entries, whose narrators are the novel's protagonists, and occasionally supplemented with newspaper clippings relating events not directly witnessed. The events portrayed in the novel take place largely in England and Transylvania during the 1890s.
The tale begins with Jonathan Harker, a newly qualified English solicitor, visiting Count Dracula in the Carpathian Mountains on the border of Transylvania, Bukovina, and Moldavia, to provide legal support for a real estate transaction overseen by Harker's employer. At first enticed by Dracula's gracious manners, Harker soon realizes that he is Dracula's prisoner. Wandering the Count's castle against Dracula's admonition, Harker encounters three female vampires, called "the sisters", from whom he is rescued by Dracula. After the preparations are made, Dracula leaves Transylvania and abandons Harker to the sisters. Harker barely escapes from the castle with his life.
Not long afterward, a Russian ship, the Demeter, having weighed anchor at Varna, runs aground on the shores of Whitby. The captain's log narrates the gradual disappearance of the entire crew, until the captain alone remained, himself bound to the helm to maintain course. An animal resembling "a large dog" is seen leaping ashore. The ship's cargo is described as silver sand and boxes of "mould", or earth, from Transylvania.
Soon Dracula is tracking Harker's fiancée, Wilhelmina "Mina" Murray, and her friend, Lucy Westenra. Lucy receives three marriage proposals from Dr. John Seward, Quincey Morris, and the Hon. Arthur Holmwood (later Lord Godalming). Lucy accepts Holmwood's proposal while turning down Seward and Morris, but all remain friends. Dracula communicates with Seward's patient Renfield, an insane man who wishes to consume insects, spiders, birds, and rats to absorb their "life force", and therefore assimilate to Dracula himself. Renfield is able to detect Dracula's presence and supplies clues accordingly.
When Lucy begins to waste away suspiciously, Seward invites his old teacher, Abraham Van Helsing, who immediately determines the cause of Lucy's condition but refuses to disclose it. While both doctors are absent, Lucy and her mother are attacked by a wolf; Mrs. Westenra, who has a heart condition, dies of fright, and Lucy dies soon after. Following Lucy's death, the newspapers report children being stalked in the night by, in their words, a "bloofer lady" (i.e., "beautiful lady"). Van Helsing, knowing Lucy has become a vampire, confides in Seward, Lord Godalming, and Morris. The suitors and Van Helsing track her down and, after a confrontation with her, stake her heart, behead her, and fill her mouth with garlic. Around the same time, Jonathan Harker arrives from Budapest, where Mina marries him after his escape, and he and Mina join the coalition against Dracula.
After Dracula learns of Van Helsing's plot against him, he attacks Mina on three occasions, and feeds Mina his own blood to control her. Under his influence, Mina oscillates from consciousness to a semi-trance during which she perceives Dracula's surroundings and actions. After the protagonists sterilize all of his lairs in London by putting pieces of consecrated host in each box of Transylvanian earth, Dracula flees to Transylvania, pursued by Van Helsing and the others under the guidance of Mina. In Transylvania, Van Helsing repulses and later destroys the vampire "sisters". Upon discovering Dracula being transported by Gypsies, Harker shears Dracula through the throat with a kukri while the mortally wounded Quincey stabs the Count in the heart with a Bowie knife. Dracula crumbles to dust, and Mina is restored to health.
The book closes with a note on Mina's and Jonathan's married life and the birth of their son, whom they name after all four members of the party, but address as "Quincey".
The original final chapter was removed, in which Dracula's castle falls apart as he dies, hiding the fact that vampires were ever there.