In his early thirties, Akufo-Addo was the General Secretary of the broad-based People’s Movement for Freedom and Justice (PMFJ), which was composed of political stalwarts such as Akwasi Amankwa Afrifa, William Ofori-Atta, Komla Agbeli Gbedemah, Albert Adu Boahen, Sam Okudzeto, Obed Asamoah, Godfrey Agama, K. S. P. Jantuah, Jones Ofori-Atta, Johnny Hanson and Nii Amaah Amartefio ("Mr. No"). This group led the "NO" campaign in the UNIGOV referendum of 1978, designed to solicit popular support for a one-party military-led State. The “No” campaign ultimately brought about the downfall of the Acheampong military government on 5 July 1978, and the restoration of multiparty democratic rule to the country in 1979. Akufo-Addo had to go briefly into exile after the referendum, when his life was in danger. But, from Europe, he could be heard constantly on the BBC World Service, fighting against the military rulers back in Ghana and calling for a return to democracy. He is acknowledged as one of the leaders of the pro-democracy movement in Ghana.
In 1991, Akufo-Addo was the chairman of the Organising Committee of the Danquah-Busia Memorial Club, a club dedicated to the preservation of the memory and ideals of the two great advocates of Ghanaian democracy, J. B. Danquah and K.A. Busia, Prime Minister of the Progress Party government of the 2nd Republic of Ghana. Akufo-Addo travelled throughout Ghana to establish branches of the Club all over the country in the grassroots style for which he is known. These branches eventually transformed into local organs of the New Patriotic Party (NPP) prior to the elections of 1992, which heralded the reintroduction of democratic governance under the 4th Republic.
In 1992, he was the first national organiser of the NPP and, later that year, campaign manager of the party's first presidential candidate, Prof. Albert Adu Boahen, the man of courage who broke the “culture of silence” in Ghana, and played such a crucial role in the reintroduction of democracy.
In 1992, Akufo-Addo set up and financed The Statesman newspaper, which has become the unofficial mouthpiece of the NPP.
In 1995, he led the famous “Kume Preko” demonstrations of the Alliance For Change (AFC), a broad-based political pressure group, which mobilised millions of people onto the streets of Ghana to protest the harsh economic conditions of the Rawlings era. Some pundits in Ghana believe that this was instrumental in re-establishing the NPP as a more formidable force after Prof Adu Boahen.
Akufo-Addo was elected three times between 1996 and 2008 as Member of Parliament for the Abuakwa South constituency in the Eastern region of Ghana. From 2001 to 2007, as Cabinet Minister, first as Attorney-General and Minister for Justice for two years, and later as Foreign Minister for five years, Akufo-Addo served in the government of President Kufuor with distinction.
As Attorney-General, he was responsible for the repeal of the Criminal Libel Law, which, hitherto, had been used to intimidate the media and criminalise free speech. The repeal has enabled the Ghanaian media become one of the most vibrant and freest in Africa. Under his chairmanship of the Legal Sector Reform Committee, the implementation of the court automation programme was initiated.
As Foreign Minister, he was fully involved in the successful Economic Community of West African States (ECOWAS) peace efforts in Sierra Leone, Liberia, Ivory Coast, and Guinea Bissau, and was chairman of the ECOWAS Mediation and Security Council in 2003.
In 2004, Ghana was elected one of the 15 pioneer members of the African Union (AU) Peace and Security Council, a mandate which was renewed at the AU Summit in Khartoum in January 2006. Akufo-Addo was chosen by his peers on the AU Executive Council to chair the Ministerial Committee of 15 that fashioned the Ezulwini Consensus, which defined the African Union’s common position on UN Reforms. He negotiated for the 2007 AU Summit to be held in Accra as part of Ghana’s Golden Jubilee celebrations, and chaired the AU Executive Council in 2007.
Ghana was elected by her peers to take the non-permanent West African seat on the UN Security Council for 2006-07. In August 2006, Akufo-Addo chaired the meeting of the Security Council which took the decision that halted Israel’s massive incursions into Lebanon. Again, Ghana was elected to the new UN body, the Human Rights Council, with the highest number of votes—183 out of 191—of any country, and as a pioneer member of another UN body, the Peacebuilding Commission.