He grew up in the provinces Agusan, Lanao, and Misamis Oriental, where he completed his elementary schooling with honors in Ateneo de Cagayan.

[1] He pursued his studies at the Ateneo de Manila University as a working student, teaching history and political science while taking up courses in law and economics.

[1] Guingona was a delegate to the 1971 Constitutional Convention and, when martial law was declared in 1972 by President Ferdinand Marcos, he resisted the abuses of the regime, serving as a human rights lawyer.

[1] When Marcos was ousted in 1986 as a result of the People Power Revolution, newly installed President Corazon Aquino appointed Guingona as chairman of the Commission on Audit, where he gained renown as a graft buster.

[1] In 1992, Guingona ran for reelection under the Laban ng Demokratikong Pilipino of Speaker of the House Ramon Mitra Jr.

In 1993, he rose to the position of majority floor leader once more, but President Fidel V. Ramos' appointment of him as executive secretary that same year ended his Senate tenure.

The decision to keep the envelope closed was ultimately made by a vote of 11–10, which heightened anti-Estrada emotions and sparked a second uprising on EDSA.

In that election, he supported the presidential and vice-presidential bids of opposition candidates Fernando Poe Jr. and Senator Loren Legarda, respectively.

After the defeat of his candidate, Fernando Poe Jr., Guingona supported the administration of Arroyo again by accepting the position of ambassador to China.

On November 29, 2007, Guingona participated in the Manila Peninsula rebellion, a mutiny led by Senator Antonio Trillanes and Brigadier General Danilo Lim that called for Arroyo's resignation.

[8] His son, Teofisto III (TG), is a former senator of the Philippines, while his daughter, Stella Marie, also served as mayor of Gingoog until 2019.