He was born in Madrid, the son of Álvaro Colón de Portugal y Portocarrero, 5th Duke of Veragua, 4th Duke of la Vega, 6th admiral of the Indies, and of Catalina de Castro y Portugal, 5th countess of Gelves, and descendant of the House of Braganza, distantly related to the Portuguese royal family.

On April 28, 1672, Enrique de Toledo y Osorio, Marquess of Villafranca was named viceroy of New Spain, but he declined the post.

He arrived at Chapultepec November 16, 1673, and remained there three weeks for reasons of health before making his entry into Mexico City.

Colón de Portugal's governorship would not last long, however, as he died on December 13 at 5 am, only five days after formally taking up the position.

His funeral was conducted with great solemnity in the cathedral, where his remains were deposited in the chapel of Santo Cristo.