Cartagena (/ˌkɑːrtəˈhɛnə/ KAR-tə-HEN-ə), known since the colonial era as Cartagena de Indias (Spanish: [kaɾtaˈxena ðe ˈindjas] ^ⓘ), is a city and one of the major ports on the northern coast of Colombia in the Caribbean Coast Region, along the Caribbean Sea. Cartagena's past role as a link in the route to the West Indies provides it with important historical value for world exploration and preservation of heritage from the great commercial maritime routes. As a former Spanish colony, it was a key port for the export of Bolivian silver to Spain and for the import of enslaved Africans under the asiento system. It was defensible against pirate attacks in the Caribbean. The city's strategic location between the Magdalena and Sinú rivers also gave it easy access to the interior of New Granada and made it a main port for trade between Spain and its overseas empire, establishing its importance by the early 1540s.

Modern Cartagena is the capital of the Bolívar Department, and had a population of 876,885 according to the 2018 census, making it the second-largest city in the Caribbean region, after Barranquilla, and the fifth-largest city in Colombia. The metropolitan area of Cartagena is the sixth-largest urban area in the country, after metropolitan area of Bucaramanga. Economic activities include the maritime and petrochemical industries, as well as tourism.

The present city—named after Cartagena, Spain and by extension, the historic city of Cartagena—was founded on 1 June 1533, making it one of South America's oldest colonial cities; but settlement by various indigenous people in the region around Cartagena Bay dates from 4000 BC. During the Spanish colonial period Cartagena had a key role in administration and expansion of the Spanish Empire. It was a center of political, ecclesiastical, and economic activity. In 1984, Cartagena's colonial walled city and fortress were designated a UNESCO World Heritage Site.

It was also the site of the Battle of Cartagena de Indias in 1741 during the War of Jenkins' Ear between Spain and Britain.

The Puerto Hormiga Culture, founded in the Arjona Municipality of the Bolívar Department in the Caribbean coast region, particularly in the area from the Sinú River Delta to the Cartagena Bay, appears to be the first documented human community in what is now Colombia. Archeologists estimate that around 4000 BC, the formative culture was located near the boundary between the current departments of Bolívar and Sucre. In this area, archeologists have found the most ancient ceramic objects of the Americas, dating from around 4000 BC. The primary reason for the proliferation of primitive societies in this area is thought to have been the relatively mild climate and the abundance of wildlife, which allowed the hunting inhabitants a comfortable life.

Archeological investigations date the decline of the Puerto Hormiga culture and its related settlements to be ~3000 BC. 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. 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. Until the Spanish colonization, many cultures derived from the Karib, Malibu and Arawak language families lived along the Colombian Caribbean coast. In the late pre-Columbian era, the Sierra Nevada de Santa Marta was home to the Tayrona people, whose language was closely related to the Chibcha language family.

Around AD 1500, the area was inhabited by different tribes of the Carib language family, more precisely the Mocanae sub-family.