The museum was founded as part of the renovation projects by the empress Maria Theresa of Austria for the University of Pavia in 1771.

In 1960, all sections were moved again into the Castle Visconteo, in order to create a unique museum which was opened to the public, but the plan was cancelled.

Versi sciolti di Dafni orobiano a Lesbia Cidonia, written by Lorenzo Mascheroni, a mathematician and a lecturer in the university.

Around 1700, Rinaldo's mummy was thrown into Lake Mantua and, in 1783, the Austrian government decided to have the hippopotamus brought to the Pavia museum.

The Geopaleontology collection[7] was stored at Visconti Castle where it was transferred there in the late 1950s until 2014, when it was moved to Palazzo Botta Adorno.

It contains over 30,000 fossil specimens — skeletal parts of invertebrates and vertebrates discovered in Po Valley — which date back the Pliocene and Miocene era.

The fossil collections include 65 slabs of fish from Bolca fossiliferous deposit, an original specimen of Ichthyosaurus (Ichthyosaurus quadriscissus) from the Mesozoic era, a pyritized crinoid from the genus Pentacrinus, as well as a complete skeleton of a cave bear (Ursus spelaeus), coming from the Alps of Lombardy.

In 1804, Napoleon Bonaparte donated the elephant skin to the Natural History Museum, at the University of Pavia, along with other zoological specimens.

Due to the museum's policies, the specimen was kept away from the public eye and remained inaccessible for more than two centuries, stored at Visconti Castle from 1960 to 2014.

It underwent careful cleaning and was subjected to major restoration work in order to repair the damage suffered over the centuries caused by mold and wear and tear.

[16] On 8 April 2017, the university arranged for an event "A Day for the Elephant" (Italian: Un giorno da Elefante) at Palazzo Botta Adorno, which included a tour of the Natural History Museum.