In 1860 the house was rented by General Bartolomé Mitre in 1860, and was his residence during his tenure as the 6th President of Argentina between 1862 and 1868.

[3] In 1868 the house was purchased and donated to Mitre by a group of local citizens in recognition of his term as president, as well as for his contributions to national unity; he lived there until his death in 1906.

La Nación, one of the nation's oldest and most influential dailies, was published here from its establishment in 1870, until 1895.

The museum's first director, Alejandro Rosa, had founded the Western Hemisphere Historic and Numismatic Society with Mitre in 1893, and following the classification of Mitre's extensive ethnolinguistic library, numismatic and other collections, the society was located in the museum from 1918 until 1971 (it was rechartered as the National Academy of History of Argentina in 1938).

The library has about 100,000 items including books, magazines, CDs, DVDs, and microfilms.