It was created in 1976, and contains one of the most important, natural and beautiful ports in the Caribbean, the bay of Portobelo, christened by Christopher Columbus in 1502, on his fourth and last voyage to the New World. The fortifications that continue to stand guard around the cove were declared a World Heritage Site by UNESCO in 1980. Found in the northern part of the isthmus on the Caribbean slope, these 70 kms. of coastal areas with palm trees and rich coral formations offer an extremely attractive and scenic landscape. During the colonial period it hosted the famous galleons fair, with their own military fortifications from the era of the conquest, which gives the area historical and cultural value and is a highlight of the national park.

The city of San Felipe de Portobelo, for which the protected area is named, was founded by Francisco Valverde y Mercado on May 20, 1597. In the mid-17th century it reached its apogee by coming to be the point of conflux for all the riches from Peru and other South American countries that arrived overland from Panama City along the Path of the Crosses.