After his brother Vazgen was assassinated, he became Prime Minister of Armenia from 3 November 1999 to 2 May 2000.

He supported the opposition leader Levon Ter-Petrosyan in the 2008 Armenian presidential election.

Prior to the 2018 Yerevan City Council election, Sargsyan co-led the Bright Alliance.

Sargsyan led the Hanrapetutyun Party as its candidate for Prime Minister in the 2021 Armenian parliamentary election.

In May 2024, Sargsyan joined the United Platform of Democratic Forces.