The museum was created in 1926 by the Provincial Council of Santander, which entrusted its management and development to Jesús Carballo García. Its inauguration was attended by Alfonso XIII. It was first housed in the Instituto de Santander building, now the Instituto Santa Clara, and in 1941 moved to the ground floor of the Palacio de la Diputación Provincial, where it remained until a few years ago.

This centre, of great international importance for the study and contemplation of prehistory, was profoundly reformed and redefined at the beginning of the 21st century, and since December 2001 has been showing rooms that mix old collections with the materials found in the most recent excavations. Both national companies, including Caja Cantabria, and international companies, especially Texnai from Japan, have collaborated in the project.

At the time, the project for the construction of the new headquarters of the Government of Cantabria, on the site where the museum and the previous headquarters were located, forced the museum to move to the ground floor of the converted Eastern Market while awaiting its definitive location. Several venues have been considered for this museum. Initially, the future Museum of Cantabria was planned to be built in the Las Llamas watercourse in Santander and later it was proposed to fit out the former headquarters of the Bank of Spain in the Cantabrian capital. Finally, in 2014, it was announced that the MUPAC would occupy the entire Eastern Market, for which it would be necessary to reach an agreement with all the commercial premises located on the first floor and recondition the building for the future exhibition spaces. In August 2016, it was confirmed that a new building would be constructed in the car park of the Palacio de Festivales next to Gamazo, where the Astilleros del Atlántico warehouses used to be.

The strong point of the Museum of Prehistory and Archaeology of Cantabria is its collection of Upper Palaeolithic movable art, one of the richest in the world. However, these are not the only pieces in the museum. The oldest remains in the museum come from the El Castillo Cave, which is over 100,000 years old. There are also Mousterian tools dating between 100,000 and 40,000 years old, as well as all kinds of pieces from the Epipalaeolithic, Chalcolithic and Bronze Age periods. As is logical, the history of Cantabria is of particular importance, with all kinds of objects from the Cantabrian people, including various giant discoid Cantabrian stelae, such as the Zurita stela.

Although the institution specialises in prehistoric archaeology, it also has archaeological remains from historical periods such as the Ancient and Middle Ages.