De Madrazo came from a Spanish family of painters. His father, Federico, was his earliest teacher. He studied at the Royal Academy in Madrid and, after 1862, in Paris with the artist Léon Cogniet. De Madrazo exhibited regularly in the Paris Salon, winning a medal at the 1878 Universal Exposition. With his brother-in-law Mariano Fortuny, he embraced genre painting, turning out small, elegant paintings of beautiful women in sumptuous surroundings. In 1882, he and his friends—the artists Giuseppe de Nittis (1846-1884) and Alfred Stevens, and the gallery owner Georges Petit—co-founded the Exposition International de Peinture to gain more exposure for foreign artists working in Paris.
In the 1890s, de Madrazo traveled to New York and remained there for several years. He continued his acquaintance with the Haggins; when he remarried in 1899, he sent Louis and Blanche an announcement. De Madrazo’s portraits were popular in New York Society. He painted industrialist Cornelius Vanderbilt II, Gertrude Vanderbilt, and collector Archer Milton Huntington, among other luminaries.