The ongoing struggle for Independence from the Spanish colonial period stalled Rivadavia's project, however, until 1823, when he promoted construction of a building for the museum as a member of Governor Martín Rodríguez's cabinet.

[1] The original museum opened in 1826 and was housed downtown in a loft inside the Santo Domingo Convent, which had been made available to host Rivadavia after his expulsion of the Dominican order from Buenos Aires.

Rivadavia also appointed a noted Italian astronomer, Ottaviano Fabrizio Mossotti, who installed the nation's first observatory, meteorological station and experimental physics laboratory during his tenure at the facility from 1828 to 1835.

Rosas' overthrow in 1852 helped lead to the creation of the Society of Friends of Natural History, who had the museum relocated in 1854 to the "Illuminated block," the former Temple of St. Ignatius and its prestigious academy maintained by the Jesuits before their suppression in 1773.

Burmeister founded the Argentine Paleontological Society in concert with the University of Buenos Aires and the Academy of Natural Sciences in Córdoba in 1870, extending the interest for the field to the nation's hinterland.

Besides the Natural Sciences Institute, the museum houses thirteen permanent exhibition halls, including an aquarium, a display with specimens collected from Argentina's numerous research stations in Antarctica, a geological collection centered on meteorites found in Argentina, a paleontology section notable for its Carnotaurus, Eoraptor, Herrerasaurus and Patagosaurus fossils, among others, and a Cenozoic paleontology display featuring Glyptodon, Macrauchenia, Megatherium and Smilodon fossils.