Darren Shan (CHRIS MASSOGLIA) is a normal teen who lives with his parents (DON McMANUS and COLLEEN CAMP) and younger sister, Annie (MORGAN SAYLOR), gets good grades and seemingly has a bright future ahead of him. That's unlike his best friend, Steve (JOSH HUTCHERSON), whose long-absent father and alcoholic mother have left him hating his life and occasionally convincing Darren to break the rules.
When the latter results in a skipped class and some broken lights at school, Darren is grounded and told he can no longer be friends with Steve. Yet, the latter convinces Darren that they should sneak off at night to attend the Cirque du Freak show downtown.
After meeting the show's manager, Mr. Tall (KEN WATANABE), the boys see a variety of acts, such as Evra the Snake Boy (PATRICK FUGIT); Rhamus Twobellies (FRANKIE FAISON) who can eat most anything; Corma Limbs (JANE KRAKOWSKI) who can regenerate severed appendages; Alexander Ribs (ORLANDO JONES) whose waist is no bigger than his exposed spine; and bearded lady Madame Truska (SALMA HAYEK).
The latter has visions of the future and sees something troubling with Darren, but she can't convince her lover, magician and poisonous spider wrangler Larten Crepsley (JOHN C. REILLY) from going out on stage. Being a fan of vampires, Steve thinks he recognizes him as one, and later tries to convince him and his friend, Gavner Purl (WILLEM DAFOE), to turn him into one. They refuse and send him on his way, but after previously getting a better look at Crepsley's spider, Darren ends up accidentally stealing the arachnid, and it ends up at school where it gets loose and bites Steve.
Realizing that the otherworldly Mr. Tiny (MICHAEL CERVERIS) and his vampanese thug, Murlaugh (RAY STEVENSON), expressed an interest in Darren's soul, Crepsley knows he must do something to keep their hands off him. Accordingly, he offers to save Steve's life in exchange for turning Darren into his half-vampire assistant who can still go out into the sunlight, but will, like other vampires, only feed off humans but not kill them, unlike the deadly vampanese.
Having faked his death so that he can stay at the Cirque camp, train with Crepsley and end up falling for teen Rebecca (JESSICA CARLSON), Darren must then contend with Steve falling in with Mr. Tiny and Murlaugh, all as the long truce between the vampires and vampanese appears coming to an end.