He was portrayed by the late Claude Rains, who also portrayed Erique Claudin in The Phantom of the Opera.
Griffin is an albino who studies optical density. His discoveries were supposed to make him famous, and he wants all the credit to himself by quitting the university he's working and continuing his experiments in an apartment. In his studies, he eventually develops a potion that renders him invisible to the human eye. During his invisible state, he tries desperately to find a cure. He steals money from people which magnetized him to the authorities. To hide when he takes residence at the Coach and Horses Inn in Ipling, Griffin steals a trenchcoat, dark goggles, bandages, and a fake nose to conceal his identity. However, he draws more attention when his experiments and billing to the local reverend arouse suspicion.
While escaping Ipling, Griffin forces a homeless man named Thomas Marvel to carry money for him. Marvel escapes the Invisible Man's clutches and runs off with Griffin's money. While in the town of Port Burdock, Griffin seeks help from a former acquaintance Dr. Arthur Kemp in aiding him in a reign of terror. Refusing, Kemp summons the local authorities including Colonel Adye who is shot dead by Griffin. Enraged and determined to punish Kemp, Griffin follows Kemp back to Ipling. Ultimately, Griffin meets his end at the hands of the mob summoned by Kemp. In death, the invisibility effect wears off and he is visible again once more.
The Universal incarnation, given the first name Jack, and unlike the novel version, Jack Griffin had a more sympathetic background. He was a researcher working in food preservation and fell in love with his employer's daughter Flora. Determined to prove himself both a successful researcher and good husband material for Flora, Griffin tests with a dangerous chemical called monocane, eventually discovering the formula for making living beings invisible. However, his applications of the formula to himself drive him to insanity.
Like in the novel, Griffin seeks aid for a megalomaniacal plot to create invisible armies from Kemp who refuses. Unlike in the novel, Griffin succeeds in killing Kemp by forcing his car to crash down a hill. He is pursued and fatally shot while trying to escape. He later dies in the hospital, apologizing for his actions and noting "I meddled in things a man must leave alone." His body becomes visible after death.
- In Alan Moore and Kevin O'Neill's series The League of Extraordinary Gentlemen, there is an incarnation of the Invisible Man called Hawley Griffin. As the character of the original novel, Griffin is a megalomaniacal psychopath whose insanity and brutality are amped. However, he finally meets his end at the hands of Edward Hyde.
- Griffin was briefly mentioned in Abbott and Costello Meet the Invisible Man, and a picture of him before the transformation (Claude Rains) is shown, though he's referred to as "John Griffin" instead of "Jack Griffin", possibly to avoid copyright.