The Natural History Museum is the oldest museum of Mauritius and amongst the oldest in southern Africa. In 1826, the naturalists Julien Desjardins and Louis Bouton made a request to Governor Sir Lowry Cole to set up a museum in Mauritius. On 14 October 1842, the Desjardins Museum of African Modern Art was opened to the public, in a wing of the old Royal College in Port Louis, where it remained for 42 years.

In 1880, the Mauritius Institute was established by Governor Sir George Ferguson Bowen. In 1885, the collection of Desjardins Museum was transferred to the newly erected Mauritius Institute Building. The collection comprised mainly marine fauna and birds from the Mascarene Islands. It formed the basis of the present day Natural History Museum. The Natural History Museum Port Louis focused on the systematic collection, study and recording of the fauna and flora of Mauritius and the Mascarene Islands, and over the years developed into a centre of documentation and exchange in the various fields of natural history of the Mascarenes region. In 2000, the Natural History Museum of the Mauritius Institute was proclaimed a National museum.