[1] Established in 1597 for its deep natural harbor, it joined Veracruz (2,066 km (1,284 mi) to the northwest) as ports used by the Spanish Empire to ship treasure from the mines of Peru (via Panama City on the Pacific side of the Isthmus and overland to Portobelo) back to Spain.

Portobelo was founded in 1597 by Spanish explorer Francisco Velarde y Mercado[2] and quickly replaced Nombre de Dios as a Caribbean port for Peruvian silver.

[4] In 1726 the British suffered a disaster in their Blockade of Porto Bello under Admiral Francis Hosier, an attempt to prevent the Spanish treasure fleet returning to Spain, when due to their lengthy wait and inactivity (as ordered by the British government) moored at Bastimentos 11 km (6.8 mi) to the northeast (not to be confused with another Bastimentos Island 270 miles to the west), the large part of the sailors died from tropical diseases.

The disaster was vindicated 13 years later when during the War of Jenkins' Ear the port was attacked and captured on November 21, 1739, by a British fleet of six ships commanded by Admiral Edward Vernon.

[5] However the Spanish soon recovered Portobelo when in 1741 they defeated Admiral Vernon in the Battle of Cartagena de Indias and forced him to return to England with a decimated fleet, having suffered more than 18,000 casualties, mostly due to disease.