He was elected as the LPRP's General Secretary on 21 March 2006, in the aftermath of the Party's 8th Congress, by the first plenum of the eighth Central Committee, succeeding Khamtai Siphandone as de facto leader of Laos.

He subsequently succeeded Siphandon as the 6th President of Laos on 8 June 2006.

In June 2011, he was re-elected as President of Laos at the seventh National Assembly.

[2] Bounnhang Vorachit was elected to succeed him as General Secretary on 22 January 2016.

[3] On 4 April 2021, Sayasone and his family were on a yacht in Nam Ngum Lake, when there was a storm and the vessel capsized.