The Mendoza family, the bearers of the title of dukes of El Infantado, embodied all their power in this building, which is the most representative property in their possession.

The original building was in the Gothic style with numerous Mudejar details, and was commissioned by the second Duke of El Infantado from Juan Guas, who started work in 1480. Later, the fifth duke adapted it to Renaissance tastes in 1569, opening up balconies on the façade, and replacing the columns on the lower floor of the Courtyard of the Lions. He also commissioned Romulo Cincinato to create frescos in various rooms; some of these paintings still survive as a unique testament to the splendour of these apartments.

After its virtual destruction in a bombing in 1936, it is most representative elements –the Courtyard of the Lions, the façade and the Garden Gallery– were restored between 1961 and 1973. It is currently the site of the Guadalajara Museum.