[1] Born into a rural family, Moscoso became active in the 1968 presidential campaign of three-time president Arnulfo Arias, following and marrying him when he went into exile after a military coup.

During the 1994 general elections for the presidency, she narrowly lost to the Democratic Revolutionary Party (PRD) candidate Ernesto Pérez Balladares by 4% of the vote.

Her popularity declined, and her party's candidate José Miguel Alemán lost to the PRD's Torrijos in the subsequent general elections to succeed her.

[2] While Torrijos ran in large part on his father's memory—including using the campaign slogan "Omar lives"[14]—Moscoso evoked that of her dead husband, leading Panamanians to joke that the election was a race between "two corpses".

She was also hampered by strict new restraints Pérez Balladares had passed on spending public money in the final days of his term, targeted specifically at her administration.

[19] Her government then faced the challenge of cleaning up environmental problems in the Canal Zone, where the US Army had long tested bombs, biological agents, and chemical weapons.

[21] Moscoso worked to end Panama's role in international crime, passing new laws against money laundering and supporting tax transparency.

[22] In December 2000, human remains were discovered at a Panamanian National Guard base, incorrectly believed to be those of Jesús Héctor Gallego Herrera, a priest murdered during the Omar Torrijos dictatorship.

[24] During her term, Moscoso was often accused of nepotism for her administrative appointments[2] and faced several corruption scandals, such as the unexplained gift of US$146,000 in watches to Legislative Assembly members.

That year, she attempted to pass a tax reform package through the Legislative Assembly, but the proposal was opposed by both the private sector and organized labor.

Shortly before leaving office, Moscoso sparked controversy by pardoning four men—Luis Posada Carriles, Gaspar Jiménez, Pedro Remon, and Guillermo Novo Sampol—who had been convicted of plotting to assassinate Cuban president Fidel Castro during a 2000 visit to Panama.

[31] Moscoso stated that the pardons had been motivated by her mistrust of Torrijos, saying, "I knew that if these men stayed here, they would be extradited to Cuba and Venezuela, and there they were surely going to kill them there.

In September 2007, she criticized the appointment as the head of the National Assembly of PRD politician Pedro Miguel González, who was wanted in the US for the murder of US Army sergeant Zak Hernández.

[34] In the same year, she joined Endara and Pérez Balladares in lobbying the Organization of American States to investigate the Hugo Chávez government's refusal to renew the broadcasting license of opposition station Radio Caracas Televisión Internacional in Venezuela.