The earliest known inhabitants of Panama were the Cuevas and the Coclé tribes, but they were wiped out by disease and fighting when the Spaniards arrived in the 16th century.

Panama was part of the Spanish Empire for 300 years (1538–1821). Spanish authorities exercised little control over much of the territory of Panama, large sections managing to resist conquest until very late in the colonial era. Because of this, indigenous people of the area were often referred to as “indios de guerra” (war Indians), and resisted Spanish attempts to conquer them or missionize them.

When Panama was colonized, the indigenous peoples who survived many diseases, massacres and enslavement of the conquest ultimately fled into the forest and nearby islands. Indian slaves were replaced by Africans.

On November 10, 1821, the Grito de La Villa de Los Santos (Cry From the Town of Saints) occurred. It was a unilateral decision by the residents of Azuero (without backing from Panama City) to declare their separation from the Spanish Empire.

In the first eighty years following independence from Spain, Panama was a department of Colombia, since voluntarily becoming part of it at the end of 1821. The people of the isthmus made several attempts to secede and came close to success in 1831, and again during the Thousand Days War of 1899–1902.

In November 1903, Panama proclaimed its independence and concluded the Hay/Bunau-Varilla Treaty with the United States. The treaty granted rights to the United States “as if it were sovereign” in a zone roughly 10 miles (16 km) wide and 50 miles (80 km) long. In that zone, the U.S. would build a canal, then administer, fortify, and defend it “in perpetuity.” In 1914, the United States completed the existing 83 km (52 mi) canal.

On September 7, 1977, the Torrijos-Carter Treaties were signed by the Panamanian head of state and U.S. President Jimmy Carter for the complete transfer of the Canal and the fourteen US army bases from the US to Panama by 1999. These treaties also granted the U.S. a perpetual right of military intervention.

Despite 1983 constitutional amendments, which proscribed a political role for the military, the Panama Defense Forces (PDF) continued to dominate Panamanian political life. By this time, General Manuel Noriega was firmly in control of both the PDF and the civilian government.

On 19 December 1988, President George H. W. Bush decided to use force against Panama, declaring that the operation was necessary to safeguard the lives of U.S. citizens in Panama, defend democracy and human rights, combat drug trafficking, and secure the functioning of the Canal as required by the Torrijos-Carter Treaties.

Operation Just Cause was justified by the United States as necessary to secure the functioning of the Canal and re-establish democracy in the country. The U.S. troops involved in Operation Just Cause achieved their primary objectives, and General Noriega eventually surrendered to U.S. authorities.

Panama’s Electoral Tribunal moved quickly to rebuild the civilian constitutional government, reinstated the results of the May 1989 election on December 27, 1989, and confirmed the victory of President Guillermo Endara and Vice Presidents Guillermo Ford and Ricardo Arias Calderon.

In 1999, Mireya Moscoso — the widow of former President Arnulfo Arias Madrid — took office after defeating Martin Torrijos in a free and fair election. Moscoso’s administration successfully handled the Panama Canal transfer and was effective in the administration of the Canal.

Martin Torrijos won the presidency and a legislative majority in the National Assembly in 2004. Conservative supermarket magnate Ricardo Martinelli was elected to succeed Martin Torrijos with a landslide victory in the May 2009 presidential election.