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Twenty-five (25) years after the Egyptian mummy Kharis (Lon Chaney Jr.) disappeared in a quicksand-laden swamp carrying the body of his resurrected lover, the 3,000 year old Princess Ananka, the Southern Engineering Company is draining the swamps for an irrigation project and unearths Kharis and Ananka (Virginia Christine), who are now being sought by Dr James Halsey (Dennis Moore) of the Scripps Museum and his associate, Dr Ilzor Zandaab (Peter Coe), who is secretly the next high priest of Arkam. After reanimating Kharis with the prescribed dose of tana leaves, Zandaab sends him out to find Ananka, with orders to kill anyone who gets in his way.

The Mummy's Curse is the fifth and final movie in Universal Studio's Mummy series, preceded by La mummia (1932) (1932), The Mummy's Hand (1940) (1940), The Mummy's Tomb (1942), and The Mummy's Ghost (1944) (1944). The movie was filmed from a screenplay written by American screenwriter Bernard Schubert based on an original story by Leon Abrams and Dwight V. Babcock.

Kharis carries the unconscious Ananka to the abandoned monastery where Zandaab has already brewed more tana fluid and is waiting to administer it to Ananka in order to lift from her the curse of immortality so that she can taken back to Egypt and given eternal rest. Meanwhile, Betty (Kay Harding) asks Ragheb (Martin Kosleck) for help finding Jim Halsey, but Ragheb leads her to the monastery instead. Once there, he informs her that Jim is not there, then turns on her with leering look. At that moment Zandaab catches Ragheb and places upon him the curse of Amon-Ra on for forsaking his vows. When Zandaab turns his back, Ragheb stabs him. Just then, Jim enters. Betty runs to him, Ragheb attempts to stab Jim, too, but Jim is able to disarm and knock him out. As Jim prepares to lead Betty back to camp, Ragheb comes to, grabs a torch, and goes after Jim again, but Kharis stops him. Attempting to get away from Kharis, Ragheb locks himself into an adjoining room, but Kharis breaks down the door, bringing down the walls of the wing upon them both. The rest of the search party arrives, and Goobie (Napoleon Simpson) notices that the remains of Ananka have turned old again. In the final scene, Jim assures Major Walsh (Addison Richards) that he will retrieve the bodies of Kharis and Ananka and send them on to the Museum and promises Betty that he'll return in order to see her again.