He studied painting under his father, Federico de Madrazo, and at the School of the Beaux Arts in Madrid. He was born in Rome, but after 1860 he lived mostly in Paris, where he studied at the École des Beaux-Arts under Léon Cogniet, and eventually established a studio. His remarkable technical ability made him a highly successful portrait and genre painter in a Salon style.
As an artist of international standing he commanded premium prices for his work. His $2,000 fee for painting Secretary Root from life moved the scale for official portraits beyond the traditional modest progressions and into 20th-century levels.