Khamphoui Sisavatdy graduated with a Bachelor of Arts in Psychology Buddhist studies from the Chulalongkorn University in 1964.

From 1964 to 1972, he was a teacher at the Buddhist Institute, Wat Ong Teu Mahawihan, a branch of Sisavangvong University.

He was a Sithandone Province House of Representative in the 7th Term Legislature of the Royal Lao Government (1972 - 1975).

When the Royal Lao Government in Exile was proclaimed on 6 May 2003, Khamphoui became its first prime minister.

Khamphoui condemned the 2006 Laotian parliamentary election and called for international pressure on Laos to install a democracy.