A combination of poor planning, famine, tropical disease and collusion between the East India Company and the Kingdom of England to frustrate the scheme led to the failure of the colony and the death of the majority of the colonists.

The town finally surrendered to a siege and blockade of the port by forces of the Spanish Empire in March 1700, and the few survivors were evacuated.

The suspension of the region, the incursions of outsiders into Guna villages in search of gold, rubber, and sea turtles, banana concessions, and colonial police abuse caused great discontent among the natives and brought the February 25, 1925 Guna Revolution, led by Nele Kantule of the town of Ustupu and Ologintipipilele (Simral Colman) of Ailigandi.

The negotiations that ended the armed conflict constituted a first step towards establishing the autonomous status of the Guna and maintaining the culture that was being suppressed.

Based on Article 5 of the Constitution of 1904, which allows for special political divisions for reasons of administrative convenience or public service, legislation on indigenous territories in Panama established the Guna District of San Blas in 1938 including areas of the provinces of Panamá and Colón.

Currently, according to the ruling of the Supreme Court of 23 March 2001, the region has a different political and administrative organization, independent of the Districts and Villages.

The Colombian political activist Jaime Bateman Cayón, founder and leader of the M-19 movement, died in Guna Yala in 1983.

Governor Erick Martelo was removed from office in September 2020 after being found traveling in a car with 75 packages of illegal drugs.

Guna Yala is politically subdivided into four corregimientos (districts), with a total of 51 comunidades (communities),[9][10] most of which are located on islands of the San Blas Archipelago off the mainland coast.

It consists of a narrow strip of land of 373-kilometre (232 mi) long on the east coast of Caribbean Panama, bordering the province of Darién and Colombia.

The Night Festival or "inna mutiki" is a party where all the people get involved in the celebration of a wedding or a new marriage in the community.

During the first twenty years of the independent country of Panama, the Kuna had serious differences with national governments, because they tried to eradicate their culture, their customs, and their disrespect, indigenous authorities wanted to strip the land apart and were outraged by the governors and the colonial police (a settler to a native, is a non-Indian).

This is linked to an incident on April 20, 1921, which was staged in the Corazón de Jesús Narganá and Westernization movement for women, which was to change clothes, take away the gold ring of the nose, the plates high carat gold, beads, winks, and coin necklaces worn as ornaments.

That day at Sugar River had an indigenous congress and there it was decided not to let the woman go, so the sahila on behalf of the community sent a message saying that the police were not looking for it.

When trying to stop some of the male relatives of women, began the battle and killed three residents of the town, two Indian policemen and others were injured with machete wildly as they fled in a canoe.

Juan Demosthenes Arosemena was the governor of the province of Colon, and was concerned about the information he had supplied the mayor of San Blas, Andrés Mojica, on a course between the indigenous independence movement, so we decided to tell the Foreign Secretary Horacio F. Alfaro, to follow closely the actions of Americans Anne Coope, missionary, and explorer Richard Oglesby Marsh.

On his return to Panama in January 1925, he found a conflict between police and indigenous ready to explode, so he asked the U.S. military intervention in the Canal Zone, to exercise a protectorate, and wrote the Declaration of Independence and Tule people's human rights and Darién.

The situation worsened until February 12, 1925, in a conference held in Ailigandi, where he met top leaders of 45 villages and tribes.

On 4 March, with the presence of the American minister, John G. South, was signed the peace agreement with the Guna, who were promised a better deal, respect for their customs, not to impose the establishment of schools, and were assured the same protection and rights enjoyed by other citizens.

The Guna, in turn, pledged to lay down their weapons, withdraw their declaration of independence, and abide by the laws of Panama.