Cartagena is served by Media Distancia trains to Valencia-Nord and Altaria services to Madrid, all via Murcia del Carmen.

Nevertheless, the railway did not commence operation until 1 February 1863, inaugurating a route that was intended to link Albacete with the Madrid-Alicante line.

The Cartagena Expansion and Sanitation Project of 1897 included in its development the final location of the station, which facilitated the start of its construction; this did not take place until the War Ministry disarmed the wall as a defensive element of the city.

The ceramicist Daniel Zuloaga stands out among the most important suppliers who worked at the station; he, under the supervision of engineer José Cebada, was responsible for the design and construction of the modernist tiling of the main façade.

In 2018, the Alvia 730 service began, enabling travel times between Cartagena to Madrid of three hours and thirty-two minutes.