He was the first president of post-Soviet Armenia born in the former Armenian SSR..

Sarkissian has been one of the longest serving ambassadors of any country to the United Kingdom, a role to which he was first appointed in 1992-1996, before returning in 1998 and 2013. He was also Armenia's maiden ambassador to the Vatican, the European Union, NATO, the Netherlands, Luxembourg and Belgium, and served as "Senior Ambassador" to Europe.

Sarkissian served as the first chairman of the Global Council on Energy Security at the World Economic Forum, with which he has had a long association. He authored numerous scientific articles and was a speaker and commentator on international affairs. His op-eds and essays have appeared in publications such as the Times, the Financial Times, the Daily Telegraph, Time magazine, Newsweek, Hollywood Reporter and the Wall Street Journal.

Sarkissian released a book titled The Small States Club: How Small Smart States can Save the World, published by Hurst Publishers in 2023 following his resignation as president the year before.In January 2023, The Small States Club was listed alongside forthcoming books by Martin Wolf and Peter Frankopan as one of the "15 books to look forward to in 2023" by the Diplomatic Courier.^[11]

Sarkissian graduated from the Yerevan State University Department of Theoretical Physics and Mathematics. He was an Honorary Doctor of the National Academy of Sciences of Armenia and member of the National Competitiveness Council of Armenia. From 1976 to 1984, he was assistant and later associate professor of Physics at Yerevan State University. In 1984, he became a visiting research fellow and visiting professor at the University of Cambridge.where he worked alongside Stephen Hawking and Lord Martin Rees.

In 1988, he established and subsequently became the Head of the Department of Computer Modeling of Complex Systems at Yerevan State University.

Sarkissian was one of the co-creators of the 1991 Tetris spinoff game Wordtris. Later packaged with Tetris as Tetris Gold, it was for a period the most popular videogame in the world by sales. In an article in The Hollywood Reporter in March 2023, Sarkissian detailed the "tense and dramatic events" surrounding the creation of Wordtris and its sale to Spectrum Holobyte. In April, he appeared on a podcast alongside Henk Rogers, the co-founder of The Tetris Company, and Alexey Pajitnov, the creator of the game, of whom he had last seen in the Soviet Union.

Before becoming president of Armenia from 2018 to 2022, Armen Sarkissian worked in science and technology, where his background included theoretical physics and co-creating the videogame Wordtris..