Gil González Dávila founded the city in 1524 and called Villa de la Natividad de Nuestra Señora, now known as Cieneguita. In 1526 Hernán Cortés came to punish González Dávila and when he arrived on Honduras' coast from Mexico and started unloading horses and cargo from the ships, several horses were drowned, and for that reason Cortés called it Puerto Caballos. By 1533, a local native leader, called Çiçumba (or Çoçumba, or Socremba, or Joamba... we don't really know since the Spanish recorded so many variants of his name) had destroyed the town, reportedly taking a woman from Sevilla, Spain captive. After Çiçumba's defeat in 1536 by Pedro de Alvarado, a new town, Puerto de Caballos was founded on the southern shore of the body of water known as the Laguna de Alvarado.
The English attacked Puerto Caballos as they did other places along the Honduran coast.Christopher Newport briefly occupied the town in the Battle of Puerto Caballos, part of the Anglo–Spanish War. Because it was vulnerable to pirates until the building of the Spanish fort at Omoa in the 18th century, it had few permanent residents in the 16th and 17th centuries. People preferred to come out to the coast from San Pedro when a ship came into port. In 1869 Puerto Caballos changed its name to Puerto Cortés in honour of Hernán Cortés.
The proposal to construct an "inter-oceanic railway" (Ferrocarril Interoceánico) in 1850, a product of the demand for transport from the Atlantic to the Pacific caused by the United States Gold Rush of 1849, began with the anchoring of the railroad at Puerto Cortés. The rail line construction had many problems. In 1876 President Marco Aurelio Soto nationalised the Trans-Oceanic Railroad, which only reached to San Pedro Sula. When the Panama Canal was completed in 1903, the alternative plan to connect the coasts was abandoned. The region became an early centre for banana production in Honduras through cultivation and export, and the port was a leader in the export of bananas.
The early banana export industry came to be dominated by foreigners; among the first foreigners to obtain a government concession was William Frederick Streich of Philadelphia in 1902. His concession was in the vicinity of Omoa and both banks of the Cuyamel River. However, in 1910 Samuel Zemurray's Cuyamel Fruit Company purchased these 5,000 acres, but soon branched out, both with more land and with political and tax concessions, especially after Zemurray installed Manuel Bonilla in office as president using mercenaries hired in the area and abroad. In addition to awarding Cuyamel additional land, Bonilla also waived the company's tax obligations. Cuyamel had built port facilities at Omoa, but also began using the facilities at Puerto Cortés and soon came to dominate them to the point that local shippers had to ask Cuyamel's permission to use the port. In 1918, Cuyamel constructed a railroad spur into Puerto Cortés, and in 1920 he obtained effective control over the National Railroad, and from this and a network of clandestine railroads the company effectively controlled all transport to the port. When Zemurray sold Cuyamel Fruit to United Fruit in 1929, the giant company had great influence in Puerto Cortés and in Honduras as a whole.
In August, Puerto Cortés celebrates its local or patronal festivities during two weeks. The last day (a Saturday) is known as Noche Veneciana (Venice's night). 15 August is a local holiday in honour of Virgen de la Asunción (Puerto Cortés local patroness or saint).
In September 2001, the Bridge Laguna de Alvarado (Alvarado lagoon) was rebuilt and inaugurated after the old bridge, a 50 years old structure, was badly damaged in 1998 by Hurricane Mitch. A concrete wall that surrounds and protects a portion of the coastline in the bay area, was built close to the north end of Bridge La Laguna, this wall is known as El Malecón, the Spanish word for 'jetty' or 'pier'.
The first four-lane highway in Honduras was inaugurated in 1996, connecting Puerto Cortés and the city of San Pedro Sula.
In 1966, the Empresa Nacional Portuaria (Honduras National Port Authority) was created. A free trade zone was created in 1976.
Among all worldwide seaports that export containers with goods with destination to USA, Puerto Cortés is the 36th in terms of volume.
Because of its proximity to US seaports in the Gulf of Mexico and on the East Coast and its seaport infrastructure, Puerto Cortés was included in the US Container Security Initiative (CSI), the first such port in Central America. In December 2005, the US government signed an agreement with Honduras's government and opened a US Customs Office in Puerto Cortés. Under this agreement, all containers exported from Puerto Cortés that are destined for any US seaport are checked by US Customs officials in Honduras.
In March 2007, under the Megaport initiative, three RPMs (Radiation Portal Monitors) were already installed in Puerto Cortés by US DOE to inspect all containers with destination to USA, checking for possible dangerous radioactive threats. On 2 April 2007 the RPMs became operative.
Puerto Cortés is home of a football team known as Platense, which in 1966 won its first Honduran National Football Champion. In 2001 the team won its second national championship. They play their home games at the Estadio Excélsior. Atlético Portuario was briefly another football club based in the city.
In 1982, a new constitution was approved; before that year mayors were designated "by finger" by Tegucigalpa top government officials.