Upon the death of Peter of Castile in 1369, Ferdinand laid claim to the vacant Castilian throne, being the great-grandson of Sancho IV through his grandmother Beatrice. However, his second cousin Henry of Trastámara, Peter's illegitimate brother, had already seized power and assumed the crown during the Castilian Civil War in 1366. The parties involved eventually accepted the mediation of Pope Gregory XI, leading to a treaty in 1371 that included Ferdinand's marriage to Leonora of Castile. But before the union could take place, Ferdinand fell passionately in love with Leonor Telles de Meneses, the wife of one of his courtiers. He swiftly arranged the dissolution of her previous marriage and made Leonor his queen, despite the serious insurrection this caused in Portugal.

Intrigues with John of Gaunt, Duke of Lancaster, further disturbed the concord between Ferdinand and Henry. John of Gaunt, who had married Peter of Castile's daughter Constance, secretly conspired with Ferdinand to dethrone Henry. The ensuing war proved unsuccessful, leading to a peace agreement in 1373. However, when Henry died in 1379, the Duke of Lancaster once again asserted his claims, finding support in Portugal. The English proved to be as offensive to their allies as they were to their enemies, prompting Ferdinand to negotiate a separate peace in Badajoz in 1382. This peace treaty stipulated that Ferdinand's daughter and heiress, Beatrice, would marry King John I of Castile, ensuring the eventual union of the two crowns.

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Tragically, Ferdinand died in 1383, leaving no male heir. The cause of his death is suspected to be poisoning. With Ferdinand's passing, the direct Burgundian line, which had held the Portuguese throne since the days of Count Henry, became extinct. This sparked the 1383-1385 Crisis, a period of war and political uncertainty. Ferdinand's illegitimate brother, John, the Grand Master of the Order of Aviz, claimed the throne, becoming the first king of the House of Aviz in 1385.

Ferdinand's ornate tomb can be admired at the Carmo Archaeological Museum in Lisbon, although his body was destroyed during the Invasions of Portugal. His legacy is intertwined with the dramatic events of his reign and the subsequent political shifts that shaped Portuguese history.

Ferdinand married Leonor Teles de Meneses, the former wife of nobleman João Lourenço da Cunha, Lord of Pombeiro, and the daughter of Martim Afonso Telo de Meneses. Their union was marred by controversy but produced no male heirs, ultimately leading to the succession crisis after Ferdinand's death.