Avramopoulos was born in Athens in 1953. He studied State Law and Political Sciences in the University of Athens, and continued his studies at the post-graduate level. After a short period of involvement as a member of the Communist Party of Greece - Interior (Greek: ΚΚΕ Εσωτερικού), a split of the Communist Party of Greece, he joined the Hellenic Ministry of Foreign Affairs Diplomatic Academy in 1980 and subsequently Greece's diplomatic corpus.
As a diplomat he served in many places:
- Within the Ministry's Diplomatic Service (1981-1983),
- as head of Greece's Consulate General in Liège, Belgium (1983-1988),
- as diplomatic adviser of Constantine Mitsotakis (1989-1991),
- as the spokesman for the Ministry of Foreign Affairs (1992),
- as head of Greece's Consulate General in Geneva, Switzerland (1992),
- and as the director of Constantine Mitsotakis' diplomatic office until 1993.
In 1993 Avramopoulos quit his diplomatic career and entered mainstream politics, first by being a candidate MP in the same year's election, and then by running for mayor of Athens in 1994, supported by the conservative New Democracy. He won easily against his opponent, Theodoros Pangalos of the social democratic PASOK. He repeated his victory in 1998 against Maria Damanaki, who was supported by both PASOK and the radical left Synaspismos, and served another four years as mayor.
His popularity as a political figure was skyrocketing, while his party New Democracy faced a lot of internal problems as Greece's primary opposition, notably the exhausting conflict between its president Costas Karamanlis and the former Prime Minister Constantine Mitsotakis. Many people of the conservative right were suggesting that he could assume a more active political role, while rumors were spreading that he would split from New Democracy and create his own party.
These rumors were confirmed in late 2001, when he established the right-of-center Movement of Free Citizens (Greek: Κίνημα Ελευθέρων Πολιτών, ΚΕΠ), known by its acronym KEP. This created an initial enthusiasm to his followers and panic to New Democracy, who seemed to lose more ground as opposition to the ruling PASOK. At the time of KEP's foundation, polls gave the new party a percentage of 24%, something extraordinary and unusual for a new party in Greece.
However, KEP's percentages in polls continued falling, and the initial enthusiasm quickly faded away. In only a few months' time, and to his supporters' surprise and disappointment, Avramopoulos unexpectedly terminated its existence as a party, pointing at KEP's financial shortcomings as an excuse. He announced that KEP would continue operating as a think tank, and this effectively marked Avramopoulos' return to New Democracy.
In the 2004 Greek legislative election, Avramopoulos was elected MP in Athens, under the flag of New Democracy. The party's leader and Prime Minister, Costas Karamanlis, selected him for the office of Minister of Tourism. After the shuffle of February 15, 2006, he moved to the Ministry for Health and Social Solidarity a position he held until New Democracy was ousted from power in the elctions of 2009.
Among the leaders in popularity polls, Avramopoulos is considered one of the most popular politicians in Greece. Always with a sober tone and a polite manner, Avramopoulos is renowned for his ability to seduce the public. His critics have questioned his political skills on many occasions, arguing that apart from his public relations skills, he has little else to show, and his opponent candidate mayor of Athens Theodoros Pangalos of PASOK has gone as far as calling him "Mr. Nothing".