[1] When Argentina became a republic after the Confederation was dissolved, Guillermo Rawson was the first Minister of Interior appointed by then president Bartolomé Mitre.

[4][2] The name of the ministry remained unchanged for over a century until the presidency of Juan Domingo Perón, when it was merged with the Justice portfolio under the administration of Ángel Borlenghi.

[10] Some particular issues that are within the ministry's jurisdiction include judging on when it is pertinent to declare a state of siege; dealing with proposals of constitutional reform and organizing constitutional conventions when it is necessary; and maintaining a state of co-operation between the governments of the provinces of Argentina and the Autonomous City of Buenos Aires, including inter-jurisdictional matters and relations, and coordinating policies that help and promote regional growth.

[10] In May 2024, the Ministery turned into a Secretariat after Guillermo Francos was appointed as Chief of Cabinet by President Javier Milei.

[13][14] The Ministry of the Interior is headquartered at 25 de Mayo Avenue 101, in the San Nicolás barrio in Buenos Aires.