Matthysen graduated from Ghent University in 1973 with a degree in Contemporary Political History.
Having joined the Belgian Ministry of Foreign Affairs in 1984, he became First Secretary at the Belgian Embassy in Bonn, then Counselor at the Embassy in then East Berlin, a position which he held through the German reunification in 1990.
In 1997 he became Head of the NATO desk at the headquarters of the Foreign Ministry in Brussels.
From 1999 to 2000, he was the Acting Head of the General Directorate for Political-Military Affairs and a senior advisor on Kosovo to the United Nations Secretary General's Special Representative for the Balkans.
In 2014 he was appointed President of the Belgian National Security Authority, and on 4 November 2014, advisor of Princess Astrid of Belgium.