Rupel was born in Ljubljana, in what was then the PR Slovenia, into a bourgeois family of former anti-fascist political emigrants from the Julian March (his grandfather was the last Slovene mayor of Duino in Austria-Hungary).

Together with other Slovene intellectuals in the 1980s, initiated and edited the alternative and dissident journal Nova Revija, which later became the platform for democratic reform in the Socialist Republic of Slovenia.

In 1989, he was one of the founders of the Slovenian Democratic Union (Slovenska demokratična zveza, SDZ), one of the first parties that opposed Communist rule.

In October 2004, this party won the election and Rupel became foreign minister in Janez Janša's centre-right government when it was approved by parliament on 3 December 2004.

After years of negotiations, disagreements and delays he signed the Agreement on Succession Issues of the Former Socialist Federal Republic of Yugoslavia on behalf of Slovenia.

In 2008, after the victory of the centre-left coalition led by Borut Pahor, Rupel was replaced as foreign minister by Samuel Žbogar.

However, he was nominated by newly elected Prime Minister Borut Pahor as his personal Special Envoy for Foreign Affairs.