In his original appearance, Imhotep was portrayed by Boris Karloff as a high priest of ancient Egypt who steals the Scroll of Thoth in an attempt to resurrect his dead lover Princess Anck-es-en-Amon.

When Ardath meets a woman named Helen Grosvenor who bears a striking resemblance to Anck-es-en-Amon, he realizes that she is a reincarnation of the princess and attempts to mummify her and make her his bride.

Imhotep, meanwhile, is condemned to endure the Curse of the Hom-Dai: the ritual involves cutting out his tongue, mummifying him alive, and sealing him in a sarcophagus filled with carnivorous scarab beetles.

During an archaeological dig in 1926 AD, Imhotep is accidentally revived when librarian and amateur Egyptologist Evelyn Carnahan (Rachel Weisz) reads the Book of the Dead at Hamunaptra, where his sarcophagus was.

Imhotep regenerates himself using the flesh of four adventurers who breached his burial-chamber and opened a cursed chest, but spares Evelyn because he wants to use her body for the resurrection of his former lover, Anck-Su-Namun.

He could also wield the ten Plagues of Egypt to an unspecified degree; in the course of the film he is shown turning water to blood, unleashing swarms of locusts, and controlling the people of the city by inflicting them with boils and sores.

Ultimately, Imhotep is defeated when he is stripped of immortality by the Book of Amun-Ra and he is stabbed with a sword by the film's protagonist Rick O'Connell (Brendan Fraser).

As he degenerates into a skeletal form and falls into the pool from which he summoned Anck-su-namun's ba, Imhotep declares the same words he scrawled into his sarcophagus thousands of years before, "Death is only the beginning", vowing that he will return to have his revenge.

In the 2001 sequel The Mummy Returns, Imhotep, having been resurrected and freed from the resin he had been trapped in at the end of the first film by a group of cultists and Anck-su-namun's reincarnation, proceeds to seek out the Bracelet of Anubis, which was the key to finding the lair of the Scorpion King, an ancient warrior whose defeat will grant Imhotep control over the Scorpion King's near-indestructible Army of Anubis.

Once Imhotep reaches the lair, he walks over a magic seal on the floor which causes him to be robbed of his telekinesis, immortality, and other powers granted by the Curse of Hom Dai by Anubis, who seemingly wishes him to face the Scorpion King as a normal mortal.

Though he was thought dead when fighting the Minotaur within the flooding catacombs, Imhotep managed to survive and strove to find other ways to conquer the world.