In 1649, as court painter to Philip IV of Spain, Diego Velázquez was sent to Rome to purchase works of art for the Alcázar in Madrid.

According to Antonio Palomino's biography of Velázquez, the painting "was generally applauded by all the painters from different countries, who said that the other pictures in the show were art but this one alone was 'truth'.

The Pope, a ruddy-faced man who would be depicted in the bright pink and crimson robes of his office, presented a tricky study in both color and composition.

Additionally, since he would be executing a portrait from life, Velázquez would be forced to work quickly while still capturing the essence of Innocent X's character.

To compensate for a restricted palette of colors, Velázquez adopted a loose, almost impressionistic style of brushwork to bring an intense vitality to his subject.

The earliest record of the ownership of the painting was in essay written in 1765 by Francisco Preciado, Director of the Royal Spanish Academy in Rome.

Hamilton sent the portrait and his other works of art to London for safekeeping, on board the ship HMS Fondroyant the flagship of Lord Nelson, when he left Naples.

[13] Velazquez's painting reinterpreted by surrealist painter Salvador Dalí in his 1960 work Portrait of Juan de Pareja, the Assistant to Velázquez which is in the collection of the Minneapolis Institute of Art.