There are several fundamental differences between the film and the original source material. For example, the comic is set in the '90s, while the film is set in 2038: Alan Moore's original story was created as a response to British Thatcherism in the early 80s and was set as a conflict between a fascist state and anarchism, whereas the film's story has been changed by the Wachowskis to fit a modern political context. Alan Moore charges that in doing so, the story has turned into an American-centric conflict between liberalism and neo-conservatism, and abandons the original anarchist-fascist themes. Moore states, "There wasn't a mention of anarchy as far as I could see. The fascism had been completely defanged. I mean, I think that any references to racial purity had been excised, whereas actually, fascists are quite big on racial purity." Furthermore, in the original story, Moore attempted to maintain moral ambiguity, and not to portray the fascists as caricatures, but as realistic, rounded characters. The time limitations of a film meant that the story had to omit or streamline some of the characters, details, and plotlines from the original story. Chiefly, whereas the original graphic novel has the fascists elected legally and kept in power through the general apathy of the public, the film introduces the "St. Mary's virus," a biological weapon engineered and released by the Norsefire party as a means of clandestinely gaining control over their own country.
Many of the characters from the graphic novel underwent significant changes for the film. For example, V is characterized in the film as a romantic freedom fighter who shows concern over the loss of innocent life. However, in the graphic novel, he is portrayed as ruthless, willing to kill anyone who gets in his way. Evey Hammond's transformation as V's protegee is also much more drastic in the novel than in the film. At the beginning of the film, she is already a confident woman with a hint of rebellion in her, whereas in the graphic novel she starts off as an insecure, desperate young woman forced into prostitution. V and Evey's relationship, strictly platonic in the original novel, develops romantically in the film, ending with mutual pledges of love. In the graphic novel's finale, she not only carries out V's plans as she does in the film, but also clearly takes on V's identity.Whereas in the film Inspector Finch sympathizes with V, in the graphic novel he is determined to stop V and goes as far as taking LSD in order to enter into a criminal's state of mind. Characters who were completely omitted from the film or had a significantly reduced role include Rose Almond, Alistair Harper, and Mrs. Heyer.
The graphic novel's main villains also underwent changes in the film adaptation. While the Chancellor within Moore's text is a brutal dictator, he is also a lonely, socially inept man who truly believes in fascism, and, in the end, wishes merely to be accepted and loved by his people. The film, however, presents none of these human qualities. Creedy, meanwhile, evolves from a relatively minor character in the graphic novel to one of the chief characters of the film adaptation; in the film, he is revealed to have been the brains behind the bioterror attack that Norsefire used to seize power. His personality is also somewhat revamped in the film; whereas he is a coarse, petty opportunist in the graphic novel, in the film he is an icy sociopath whom V calls "a man seemingly without a conscience, for whom the ends always justify the means."
The setting and plot of the film were also changed from the original story. Whereas the film only mentions the United States' civil war and collapse, in the graphic novel, it is mentioned that a global nuclear war has destroyed much of the world outside of Britain. With a nuclear winter causing famine and massive flooding, there is a real fear that a collapse of the Norsefire government would lead to disaster. Whereas the film ends in a relatively peaceful overthrow, in the graphic novel there is a violent collapse of authority. Other differences include the computer system "Fate", which is completely missing from the film. (In the original story, Fate was a Big Brother-like computer which served as Norsefire's eyes and ears and also helped explain how V could see and hear the things he did) V's terrorist targets are also different in the graphic novel, as he destroys Parliament and the Old Bailey in the beginning, and destroys 10 Downing Street for the finale.