The history of the institution now known as the Museo de Cádiz began with the Ecclesiastical Confiscations of Mendizábal in 1835, when a number of paintings removed from different secularised monasteries and convents were handed over to the city’s Academy of Fine Arts. Among them was the Zurbarán series from the Carthusian monastery in Jerez de la Frontera. In 1887, the chance discovery of a Phoenician male anthropoid sarcophagus on lands owned by the Cádiz shipyards laid the foundations of the archaeology collection and justified the creation of a city museum to house such artefacts, which grew as archaeological excavations continued to unearth new finds.

The museum has had several homes over the years, operating out of Callejón del Tinte and Paseo de Canalejas before finally moving into the building in Plaza de Mina in 1935. Initially, it only occupied the ground floor and shared the space with the Academy of Fine Arts, although the archaeological and fine arts museums remained separate institutions, each with their own director and staff. It was not until 1970 that the two merged to form the current Museo de Cádiz, which also included an Ethnography Section.