Manuel de Moura y Corte Real was the second of three marquises named Castelo Rodrigo. Although the family served the King of Spain, it was Portuguese and its roots were in Lisbon. The family traced its origin to the reconquest of Moura (Alentejo, Portugal) from the Moors, during the Reconquista in 1165, but its fortune was established in the late sixteenth century, when Cristóvão de Moura (1528-1613), the first Marquis of Castelo Rodrigo backed the claims of the Spanish king, Philip II, to the throne of Portugal. As agents of the Spanish crown, the family gained wealth and prominence.
Manuel de Moura y Corte Real married Leonor de Melo. His oldest surviving son and heir, Francisco de Moura, destined to become the third Marquis of Castelo Rodrigo was born in 1610. Like his father, he eventually became governor of the Southern Netherlands.
Manuel entered the service of the Habsburg crown in 1615 as Gentleman of the Chamber of the future Philip IV. When the prince succeeded to the throne as Philip IV in 1621, Castelo Rodrigo was kept on the sidelines by his jealous rival Gaspar de Guzman Olivares, still insecure in his position as favorite.
Castelo Rodrigo was transferred back to Lisbon to arm a fleet in 1627, but was recalled to court temporarily in 1630, when Olivares decided to put his rival to use in the service of Habsburg diplomacy. Castelo Rodrigo was appointed ambassador to Rome, where he was a patron to Borromini and the sculptor François Duquesnoy.
Castelo Rodrigo's embassy came to an end with the revolt of Portugal in December 1640. He remained unswervingly loyal to the Spanish Habsburg crown, suffering extensive losses of family lands in Portugal, Even so, it was impolitic to have a Portuguese serving as a Spanish ambassador during the revolt, and Olivares was not completely sure of his Castelo Rodrigo's loyalty.
In 1642, he was sent to Vienna, where he served until May 1644. From June 1644 he served in Brussels as adjunct governor of the Netherlands. He worked for the cause of peace between the United Provinces and Spain, and was instrumental in the preliminary negotiations which set in motion the peace conference of Münster. He served as Philip IV's trusted minister until his recall in 1647.
Castelo Rodrigo arrived in Madrid on 14 January 1648, where he is recorded in 1649 in the position of majordomo in the royal palace. A portrait formerly ascribed to Velázquez shows him bearing his age with dignity . He died in Madrid in 1651 at the age of 61.