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Cartagena was founded about 227 BC by the Carthaginian general Hasdrubal as Qart Hadast, Punic for "new city". Hasdrubal extended the newly acquired Carthaginian empire in Iberia by skillful diplomacy, and consolidated it by the foundation of Qart Hadast in an excellent haven as the capital of a new province. Hannibal got silver from the mines there to carry on the war against Rome.

When it was taken by the Roman general Scipio Africanus Major in 209 BC it was renamed as Carthago Nova, Latin for "New Carthage" (which is somewhat humorous, as "Carthago" is a Latinization of "Qart Hadast," thus unknowingly the Romans named the city "New New City"). At the time Carthago Nova was said to be one of the richest cities in the world. The city gave its name (without the 'new') to the newest province in the Hispaniae diocese, in the form of an adjective: Carthaginiensis.

In 1873, the garrison arose against the First Spanish Republic and formed the independent Cartagena Canton. Since they had the best part of the Spanish Navy, they cruised the Spanish Mediterranean trying to bring them to Cantonalism. The Federalist Spanish government declared them a pirate fleet, encouraging foreign countries to chase and sink them.