Karen Karapetyan was born on 14 August 1964 in Stepanakert, then administrative center of the Nagorno-Karabakh Autonomous Oblast․ However, he grew up and was raised in Yerevan.

From 1985 to 1996, he worked in the computing center of the State Planning Committee of Armenia, as well as in the Association of Scientists and Cultural Workers and taught at YSU.

He succeeded Gagik Beglaryan, a controversial mayor who resigned in early December 2010 after being embroiled in a high-profile scandal with the presidential administration of Serzh Sargsyan.

Just one month into his term as mayor, Karapetyan arguably sparked the 2011 Armenian protests when he ordered the municipality to enforce a strict ban on street trading.

His term ended on 17 April 2018, when former President Serzh Sargsyan was named Prime Minister, in a move that opposition groups denounced as a power grab.