Predestination is a central pillar of Branhamist theology. William Branham taught a stringent form of Calvinist predestination: God has eternally foreordained who will be saved and who will be lost. The saved are identified as the 'bride of Christ'—a predestined elect group prepared for rapture and exaltation. The reprobate are the 'serpent seed'—those without the divine seed—who are foreordained to destruction.

This doctrine is intertwined with Branham's serpent seed cosmology: Cain and his descendants, offspring of Eve and the Serpent, represent the reprobate line eternally cut off from salvation. While God extends mercy and the offer of grace to all through the Gospel, only those whose election was settled before the foundation of the world can truly repent, believe, and receive the Message. Free will operates within the boundaries of eternal predestination.