The city was founded on June 1, 1533, and named after Cartagena, Spain, which in turn was named after Carthage in Tunisia.
Settlement in the region around Cartagena Bay by various indigenous people dates back to 4000 BC.
The Monsú people's diet was based mostly on shellfish and fresh and salt-water fish.The development of the Sinú society in what is today the departments of Córdoba and Sucre, eclipsed these first developments around the Cartagena Bay area.The primary reason for the proliferation of primitive societies in this area is thought to have been the relative mildness of climate and the abundance of wildlife, which allowed the hunting inhabitants a comfortable life.Archaeological investigations date the decline of the Puerto Hormiga culture and its related settlements to around 3000 BC.Archaeologists estimate that around 4000 BC, the formative culture was located near the boundary between the present-day departments of Bolívar and Sucre.
In this area, archaeologists have found the most ancient ceramic objects of the Americas, dating from around 4000 BC.
A major attraction was the gold found in the tombs of the Sinú Culture.
the city had fewer than 2000 inhabitants and one church; the dramatically increasing fame and wealth of the prosperous city turned it into an attractive plunder site for pirates and corsairs–French and English privateers licensed by their king.
The rise of a much more developed culture, the Monsú, who lived at the end of the Dique Canal near today's Cartagena neighborhoods Pasacaballos and Ciénaga Honda at the northernmost part of Barú Island, has been hypothesized.
The Monsú culture appears to have inherited the Puerto Hormiga culture's use of the art of pottery and also to have developed a mixed economy of agriculture and basic manufacture.
Thirty years after its founding, the city was pillaged by the French nobleman Jean-François Roberval.