He previously served as congressman for Santander as senator, Inspector General of Colombia, president of the National Constituent Assembly, Minister of the Interior, and as ambassador to the Organization of American States.

After graduating as a lawyer from the Universidad del Atlántico in Barranquilla, Serpa went back to his native Santander Department and became a judge for the town of Tona.

Serpa was later elected to the National Constituent Assembly in 1991 in which he shared a collegiate presidency with Antonio Navarro Wolff (former member of the M-19 guerrillas) and Álvaro Gómez Hurtado (representative of the Conservative Party) to create the Colombian Constitution of 1991.

During the government of Álvaro Uribe, Serpa was appointed ambassador of Colombia to the Organization of American States (OAS) and he also disputed the presidential bids of 2002 and 2006.

In 1981 Serpa met Ernesto Samper Pizano, who was working as debate chief of Alfonso López Michelsen's second presidential campaign, and became good friends.

For the presidential campaign of 1990 Samper became a candidate and Serpa collaborated with his efforts in the Santander Department, his region of influence, while being the leader of his movement: the FILA.

On 20 June 1994, the opposing presidential candidate Andrés Pastrana then made public the Narcocassettes a series of telephone recordings in which members of the Cali drug cartel mainly journalist Alberto Giraldo talked with Gilberto and Miguel Rodríguez Orejuela regarding the financing of the Samper campaign for the presidency.

After this incident Serpa's credibility maintained a low level with Colombians for supporting Samper, as well as responding to criticism with aggravating words.

During the government of Belisario Betancur, Serpa was invited to be a negotiator between the ELN guerrillas and was part of numerous peace commissions that never achieved successful results.

A few years later he changed his position and after quitting his post as ambassador to the Organization of American States (OAS), he decided to run again for the presidency.