In early 1553, Edward VI's health declined after a feverish cold developed into incurable pulmonary tuberculosis. At sixteen years of age, the young king had not yet married or had children of his own. Without children to inherit the throne, Edward VI was supposed to be succeeded by Mary and her heirs followed by Elizabeth under the terms of the Third Succession Act. However, with the influence of Northumberland who was his Protector at the time, the king decided that his half-sisters' claim was illegitimate and the throne should be passed to the descendants of Henry VIII's sister, particularly to the children of Frances Brandon, Duchess of Suffolk.

Changes made in Edward VI's plan included outlining the succession if he were to die childless. Initially, the king assumed that there would be time for a son and heir to be born to the Duchess of Suffolk or her eldest daughter Lady Jane Grey. When it became clear that there would be no time for that as Edward was dying, the devise was ultimately changed.