When João III died in 1557, the only surviving heir to the throne was his three-year-old son, Sebastião, who took over the government at the age of fourteen. Sickly and poorly educated, Sebastião proved to be mentally unstable, and as he grew to young manhood he developed a fanatical obsession with launching a great crusade against the Muslims in North Africa, thus reviving the Moroccan policy of Afonso V. In 1578, when he was twenty-four years old, Sebastião organized an army of 24,000 and assembled a large fleet that left Portugal on August 4 for Alcázarquivir. Sebastião's army, poorly equipped and incompetently led, was defeated, and the king, presumed killed in battle, was never seen again. A large number of the nobility were captured and held for ransom. This defeat, the most disastrous in Portuguese military history, swept away the flower of the aristocratic leadership and drained the coffers of the treasury in order to pay ransoms. Worse, it resulted in the death of a king who had no descendants, plunging Portugal into a period of confusion and intrigue over the succession.

With Sebastião's death, the crown fell to his uncle, Henrique, the last surviving son of Manuel I. This solved the succession crisis only temporarily because Henrique was an infirm and aged cardinal who was unable to obtain dispensation from the pope to marry. There were several pretenders to the throne, one of whom was Philip II of Spain, nephew of João III.

When Henrique died in 1580, a powerful Spanish army commanded by the duke of Alba invaded Portugal and marched on Lisbon. This force routed the army of rival contender, António, prior of Crato and the illegitimate son of João III's son Luís. Portugal was annexed by Spain, and Philip II was declared Filipe I of Portugal.

Data as of January 1993