In the deuterocanonical Book of Judith, Holofernes is an invading general of Nebuchadnezzar, who dispatched Holofernes to take vengeance on the nations of the West that had withheld their assistance to his reign. Holofernes occupied all the nations along the sea coast and destroyed all the gods of the nations, so that all nations would worship Nebuchadnezzar alone. Holofernes was warned by Achior, the leader of the children of Ammon, against attacking the Jewish people. Holofernes and his followers were angered by Achior. They rebuked him, insisting that there was no god other than Nebuchadnezzar.
The general laid siege to Bethulia, commonly believed to be Meselieh, and the city almost surrendered. Holofernes's advance stopped the water supply to Bethulia. The people lost heart and encouraged Ozias and their rulers to give way. The leaders vowed to surrender if no help arrived within five days.
Bethulia was saved by Judith, a beautiful Hebrew widow who entered Holofernes's camp and seduced him. Judith then beheaded Holofernes while he was drunk. She returned to Bethulia with the severed head, and the Hebrews defeated the enemy.