He studied law at the Universities of Athens, Milan and Cologne where he submitted his PhD thesis on Private International Law. He worked for the Munich Institute for South-Eastern Europe. He is the author of a volume on the Greek resistance movement against the Nazis, published by the prestigious German publishing house Surkamp, as well as of a number of studies and articles that have appeared in foreign newspapers and magazines.

The 1967 military coup found him in Western Germany. He was among the founders of the Socialist Democratic Union which organized and mobilized Greeks working and studying in Western Europe against the colonel's junta. He was also a founding member of the first trade union resistance organization and broadcast regularly from Deutsche Welle radio.

Since December 1974 he has been continually elected to the PASOK Central Committee. He was also member of the Coordination Council, the Executive Bureau and the Political Secretariat, as well as Secretary of the PASOK International Re1ations Committee from April 1975 to 1985. For a number of years he was also a member of the Coordinating Committee of the Socialist and Progressive Parties of the Mediterranean. He was first elected to Parliament in 1977 and represented Ioannina continuously until the 2004 election.

From 1981 to 1989 and from 1993 to 1996, during the Andreas Papandreou governments, he was undersecretary, Deputy Minister and finally Minister of Foreign Affairs. During the Zolotas all party government he was Deputy Minister of Defence.

In the C. Simitis administration he was for a number of years Chairman of the Standing Committee on Defence and Foreign Affairs of the Hellenic Parliament.

During his long career as a Minister, he identified himself with a foreign policy that was clearsighted and comprehensive. In the 80's he played a key role in trying to bring about a solution to the problem of the Middle East. This culminated in the successful mediation for the safe departure of the trapped Palestinian resistance fighters and Arafat himself from Lebanon, on board Greek vessels in 1983.

He paid particular attention to the creation of sound relations with the Arab world and achieved, among other things, the normalisation of relations between Greece and Egypt and the establishment of the tripartite cooperation of Iran, Armenia and Greece. He held talks with a total of 12 Turkish Foreign Ministers and was firmly committed to the continuous and difficult effort to normalize Greek-Turkish relations. This culminated in the signing of the Papoulias-Yilmaz memorandum in 1988.
He supported Turkey's European aspirations conditional on their respect for international law and European Union values.

In the period 1993-1996 and particularly at the crucial Essen Summit he played an important role in starting accession talks between the Republic of Cyprus and the European Union.

As president-in-office of the European Union and member of the contact group for the former Yugoslavia, together with Warren Christopher, Klaus Kinkel, Alain Juppe, Andrei Kosyrev and Hans Van Der Brook, he spared no effort to bring about a resolution of the crisis in Bosnia- Herzegovina. He signed the Interim Agreement with the Former Yugoslav Republic of Macedonia (FYROM), aiming at the establishment of better relations between the two countries. He has always kept channels of communication open with all Balkan leaders and has repeatedly mediated on behalf of the EU.

He was very interested in relations between Greece and the Balkan states and it was upon his initiative that the first meeting of the Foreign Ministers of the Balkans was organized in Belgrade in 1988. There, he began talks with Bulgaria and the then Soviet Union on the Burgas- Alexandroupolis oil pipeline.

He was responsible for the signing of the protocol of mutual civil and military assistance with Bulgaria in the 80's. He restored friendly and neighbourly relations with Albania by ending the state of war between the two countries.

Karolos Papoulias has always been very supportive of any step towards detente, peace and disarmament e.g. the "Initiative of the Six" for peace and disarmament, the participation of Greece in the Conference on Disarmament and Peace in Europe and in the Conference for the Abolition of Chemical Weapons, his proposals to create a nuclear-free zone in the Balkans and the promotion of the idea of making the Mediterranean a sea of peace and cooperation. The JANNINA 1 tripartite cooperation conference, between Greece, Bulgaria and Romania, was his idea and he was a strong supporter of the Black Sea Conference, which he also chaired.
With his visit to Washington in 1985 and the return visit of Secretary of State George Shultz, he made an important contribution to the redefining and improvement of Greek-American relations which had gone through a delicate phase during the previous years.

He is a founding member and, was until recently the president, of the Association for the Greek Linguistic Heritage.
He speaks German, French and Italian.
He was Greek pole-vault champion, member of the national volley-ball team and president for twenty five years of the historic Ethnikos athletic union.

He is married to May Panou and has three daughters.