This is a list of notable alumni of Mfantsipim School.
- Kobina Sekyi - President, Aborigines' Rights Protection Society (ARPS), lawyer, writer, author of The Blinkards
- Kofi Abrefa Busia - Prime Minister of Ghana
- William Ofori Atta - Member of "The Big Six"
- Joseph W.S. de-Graft Johnson - Vice President of Ghana (1979–1981)
- John C. de-Graft Johnson - Ambassador in The Hague (1967–1970)
- Kow Nkensen Arkaah - Vice President of Ghana (1992–1996)
- Kwesi Amissah-Arthur - Vice President of Ghana (2012–2017)
- Albert Adu Boahen - first presidential candidate of the New Patriotic Party (NPP). Flagbearer in the 1992 general election
- Joseph Ephraim Casely-Hayford - lawyer and politician and member of Fante Confederacy and Aborigines' Rights Protection Society
- Papa Owusu-Ankomah - former MP for Sekondi (7 January 1997 – 6 January 2017), and Minister of State (2001–2008).
- Samuel Atta Mills - Member of parliament for the Komenda-Edina-Eguafo-Abirem Constituency (2017–)
- Kwabena Agyapong - politician, former General Secretary of the NPP
- Boakye Agyarko - former Minister for Energy, Ghana
- George Emmanuel Kwesi Aikins - former Attorney General of Ghana
- Kwabena Kwakye Anti - Minister in the second republic
- Joe Appiah - politician
- Albert Bosomtwi-Sam - MP for Sekondi (1992 to 1996)
- Francis Yao Asare - Minister in the first republic
- Kwaku Boateng - minister in the first republic
- T. D. Brodie-Mends - minister in the second republic
- Archie Casely-Hayford - lawyer and politician
- Isaac Chinebuah - academic and politician
- Alexander Apeatu Aboagye da Costa - deputy minister in the Busia government
- Alfred Jonas Dowuona-Hammond - Minister in the first republic
- Kwaku Baah - Deputy Minister in the Busia government
- Kwamena Bartels - Minister of state in the Kufuor government
- Justice Akuamoa Boateng - deputy minister in the Busia government
- Kwamena Duncan - Central Regional Minister, Akufo-Addo government
- John Kofi Fynn - Deputy Minister in the Busia government
- Ashford Emmanuel Inkumsah - minister in the first republic
- J. Kwesi Lamptey - minister in the second republic
- Kofi Asante Ofori-Atta - politician, former Speaker of the Parliament of Ghana
- J. V. L. Phillips - Minister in the NLC regime
- Augustus Obuadum Tanoh - founding member of the National Democratic Congress, founder of the National Reform Party and presidential candidate in the 2000 Ghanaian general election
- Emmanuel Gyekye Tanoh - Minister of state in the PNDC regime
- Samuel Atta Mills - Member of Parliament for Komenda Edina Eguafo Abrem from 2016 to present
- Kofi Annan - former UN Secretary General
- Mohamed Ibn Chambas - former MP and diplomat
- J. L. S. Abbey - former diplomat
- James Aggrey-Orleans - former Ghanaian envoy to the UK
- Francis Lodowic Bartels - former diplomat
- Ebenezer Moses Debrah - former diplomat
- Patrick R. D. Hayford - former diplomat, Ghana's Ambassador to South Africa (1997–1999)
- Alex Quaison-Sackey - first black president of the UN General Assembly
- Nana Effah-Apenteng - former permanent representative of Ghana to the United Nations
- William George Mensah Brandful - retired diplomat
- Papa Owusu-Ankomah, diplomat, 2017 to date
- Miguel Augustus Francisco Ribeiro - former diplomat
- Eric Kwamina Otoo, former diplomat
- Yaw Bamful Turkson, career diplomat and Ambassador(1957-1988)
- Nini Olufemi Akilaja Akiwumi,UN International Civil Servant (UNHCR - High Commissioner's Representative to Russia, Sudan, Papua New Guinea and Sierra Leone) and Ghana's Ambassador Plenipotentiary to Egypt, Lebanon, Cyprus and Sudan 2004 to 2008.
Business, banking and finance
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Military and law enforcement
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- Kofi Amoa-Abban - Founder of Rigworld
- Herman Chinery-Hesse - Founder of SOFTtribe, the largest software company in Ghana
- Isaac Sesi - Entrepreneur, Engineer, and Founder of Sesi Technologies
- Edward Annan - Co-owner and Co-founder of Ghanaian domestic airline, Passion Air and Founder of Masai Motors Limited
- Kwasi Twum - Owner and CEO of The Multimedia Group, Ghana's largest independent commercial media group
Arts and entertainment
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Athletics and sports
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