In Nosferatu, Graf Orlok (who is in actuality the vampire Nosferatu) poses as a nobleman from the Carpathian Mountains who moves to the fictional city of Wisborg, Germany, and brings death with him. He lives in a vast castle high in the mountains, which is badly neglected and has a highly sinister feel to it. Local townsfolk refuse to go anywhere near his castle. Orlok is visited by the film's protagonist, the young Thomas Hutter, the assistant of a Wisborg estate agent, who travels to his castle to show properties for sale in Wisborg. Orlok conceals himself in one of his soil-filled coffins and is loaded onto a ship bound for Wisborg. On board the ship, he kills every crew member until only the captain and his first mate remain. Later when the first mate goes to the cargo hold to investigate, Graf Orlok rises from his coffin, terrifying the first mate who jumps overboard in fear. The captain ties himself to the wheel of the ship when Graf Orlok creeps up on him and kills the captain. Upon his arrival in Wisborg, he spreads disease and plague, forcing the local authorities to declare a quarantine and provoking hysteria amongst the citizens. At the end of the film, Orlok attempts to attack Hutter's young wife in her room, but is caught unaware by the rays of the rising sun, which burn him away in a cloud of smoke.
Orlok is the main model for a style of fictional vampire that is often nicknamed "nosferatu" after the movie. Although based upon Count Dracula, Orlok possesses none of his predecessor's aristocratic charm or seductiveness. His face and ears resemble that of a bat's, his nails are long sharp claws and is much more analogous to historical folklore accounts of vampires. He sleeps in soil infected with the Black Death, and brings plague and disease with him. He is followed everywhere by rats, traditional carriers of the feared Black Death. In terms of horror movie stereotypes, other vampires based upon this character are creatures bordering between a vampire and a mutant.
- The 2000 film Shadow of the Vampire presented a fictional account of the filming of Nosferatu in which Schreck (played by Willem Dafoe) is actually a vampire.
- In Kim Newman's Anno Dracula, Orlok serves in the Carpathian Guards of Dracula and is the Governor of the Tower of London. Orlok appears as part of the German forces, along with other silent film characters such as Doctor Caligari and Doctor Mabuse, trying to create the Red Baron in Newman's sequel, The Bloody Red Baron.
- In the roleplaying game Vampire: the Masquerade, the Nosferatu are closely based on Graf Orlok, although no two Nosferatu look alike (they are simply unbearably ugly). In the television series Kindred: The Embraced (which was based on Vampire) the appearance of the Nosferatu is uniform and they all resemble Orlok.
- Orlok has also been featured on several occasions in the popular Castlevania video game series. First, he served as a boss in Castlevania: Symphony of the Night, in which he is referred to as Olrox (in the Japanese version of the game, his name is Orlock). Also, in Castlevania: Aria of Sorrow and Castlevania: Dawn of Sorrow, Olrox's Suit can be equipped as an armor.
- In the anime TV series Hellsing, the antagonist Incognito's appearance seems to be based on that of Graf Orlok. By contrast, Alucard is based on the more popular imagery of the suave Dracula.
- Orlok was portrayed under the name "Nosferatu" in the highly popular SpongeBob SquarePants TV show, where at the end of the episode "The Graveyard Shift" he was shown turning a light switch on and off.
- Additionally, Californian grindcore band Graf Orlock took their name from the character.
- The TV show Are You Afraid of the Dark? episode "The Tale of the Midnight Madness" had Orlok coming out of the film.
- The It's Alive Show is a TV program broadcasting weekly out of Pittsburgh, Pennsylvania and showcasing horror and science fiction B movies along with trivia and comedy skits. Cast member Hellga Scheidenentzündung is a mute female nosferatu who closely resembles a diminutive and silent Orlok.
- In the Angel episode Why We Fight, a Nosferatu-like vampire appears.
- In the book Carpe Jugulum by Terry Pratchett, one of the Magpyres' (who, for the record, is extremely fair and allows himself to be killed occasionally)ancestors is described as looking like Graf Orlok.
- The 2014 Film What We Do In The Shadows features Petyr, an 8,000 year old vampire who resembles Graf Orlok.