The history of the department was represented in documents, weapons, flags and other items from the time of Colombian independence to the Thousand Days' War.

In 1946, Teresa Santamaria de Gonzalez and Joaquin Jaramillo Sierra, of the Honor Society for the Betterment of Medellín were concerned that the city did not have a representative museum.

In 1953, the museum received legal status, and it finally opened in 1955 in the Casa de la Moneda (Coin House), itself a former aguardiente factory.

Since 2016, with the arrival of María del Rosario Escobar as the director, the Museum of Antioquia has undertaken the project Museo 360 seeking to outline the museum as a space for encounters and reflections that “recognize the reality of the city, instead of hiding it.”[1] Museo 360 aims to ”settle historical debts of exclusion, discrimination“ and to overcome “the inability to understand the other, amid the fear of being different.”[1] According to Escobar, the museum's mission is to “review history and its stories, and create new stories that are inclusive and allow us to understand that the problems of the city and its protagonists exist.”[1] This institutional approach seeks to provoke reflections on the historical paths that have led to the present of a society, and the role that cultural institutions play in these processes.

Accordingly, the curatorial strategy of the permanent galleries invites visitors to inquire about the role of art history and museums in the reinforcement of exclusionary social constructs.

[2][2] Nadie sabe quién soy yo was the beginning of a series of curatorial and educational collaborations between Las Guerreras del Centro and the Museum of Antioquia.

Such collaborative projects constitute destigmatizing and empowering critical museology practices that generate new spaces for exchanges and social dialogues within and outside of the museum.