The Naval Museum of Cartagena was opened on July 8, 1986. The original building was built under the direction of the architect Lorenzo Ros in 1926. Originally the building was used by the School of Apprentices of the Spanish Society of Naval Construction. They changed its name in 1947 to National Company Bazán. Later it became the school Our Lady of the Rosary. Later the Navy reclaimed the building and converted it to the naval museum. Captain Luis Delgado Bañón was director until January 8, 2011, when he retired. The current director is the captain of ship Jorge Madrid.

The museum has been moved to a new headquarters in the city's seafront, in the former Maritime Instruction Headquarters, a historical building from the mid-eighteenth century that was constructed by the military engineer Mateo Vodopich. The building is in front of the Botes Basin. Since its construction in 1786, it has been the State Penitentiary Center (1824), Presidio (1910), and after the Spanish Civil War Barracks for the Instruction of Sailors. Following the agreement signed in 2005 by the Ministry of Defense, the Autonomous Community of the Region of Murcia and the Polytechnic University of Cartagena, the use of the building is shared between the university and naval museum. The space dedicated to the museum is in the southern half of the ground floor of the building.