During his father's presidency, he was a student in Colegio San Carlos. He got a degree in law at the Universidad del Rosario in 1977. After obtaining a postgraduate in Harvard in the United States, he returned to Colombia. On his return he founded a magazine called Guión and a television news program called Noticiero TV Hoy. As a regular news anchor he became a nationally known figure.
In 1982 he formally began his political career, gaining a seat on the local Bogotá council. He also specialized in press articles on the production and trafficking of cocaine, for which he gained many journalistic awards. In 1991 he was elected Senator.
He was kidnapped on 18 January 1988 in Antioquia by the Medellín drug cartel, which was pressuring the Colombian government into preventing the extradition of Pablo Escobar and other drug lords to the United States. He was found by the National Police a week later, and in March he was elected mayor of Bogotá, a position he held until 1990. He gained a reputation for strengthening security and reducing crime.
In 1994 he stood for the presidency against Liberal candidate Ernesto Samper, losing by only 2 points in the second round. Pastrana immediately accused Samper of using drug money to finance his campaign, and provided audio recordings to the authorities which subsequently attracted much media attention and eventually led to a scandal known as 8.000 Process (Proceso 8.000).
While this accusation underwent a parliamentary investigation, Pastrana retired into his private life. In 1998, Pastrana announced his intention to run for President. This time he won in the Presidential elections of 1998.
His presidency is remembered first for his negotiations with the two left-wing guerrilla groups FARC and ELN, culminating in the grant of a demilitarized safe haven to the guerrillas the size of Switzerland, and second for his breaking off said negotiations. It is also remembered for a growing degree of unpopularity in polls as his term progressed. Some critics accused him of possibly accepting unspecified bribes from leading FARC and ELN members, but no concrete evidence of that was presented during his presidency. His administration proposed and initially oversaw the implementation of the controversial Plan Colombia aid package and anti-drug strategy. He was also very criticized for all the seemingly pleasure trips he took around the world during his term.
In 2005 President Uribe, who had been a critic of Pastrana's peace process with the FARC and had received criticisms from Pastrana regarding his negotiations with Colombian paramilitary groups, surprisingly offered the former president the post of Ambassador to the United States in Washington DC. After consulting his family and political supporters, Pastrana accepted.
Some political analysts theorized that Uribe considered that Pastrana would be a useful diplomat in Washington, because he would help to renegotiate Plan Colombia and in general to maintain U.S. aid to Colombia, which has contributed to the successes of the Uribe administration.
In July 2006, a few days after President Uribe had appointed former president Ernesto Samper as Colombian ambassador to France, Pastrana told the President that he was "morally impeded" to participate in a government along with former president Samper. Pastrana resigned and returned to Colombia and Samper rejected his own appointment.