The initial plan for the Museum's current building dates back to 1942 and was the work of the architects Luis Moya and Luis Martínez Feduchi. Work began in the same year, and the building partially opened in 1965.
The new building, in line with the ideas behind the Museum’s founding decree, was intended to suggest the idea of Spain's evangelical mission and acculturating work in the Americas. For this reason, it was conceived in a historicist style, with a tower suggestive of American baroque churches and a convent-like layout. This layout can be seen both in the exhibition rooms, which are arranged around a landscaped central cloister, and in the adjoining service building, which is structured around a courtyard that has since been converted into a reading room.
However, not all of the planned parts - such as the present cloisters and the north-west corner - were actually built. Construction of the building was completed in the 1980s and early 1990s, and the Museum as we know it today opened in 1994.