Mfantsipim was the first secondary school to be established in the Gold Coast (now Ghana) in 1876 and in 1905, it moved to its present location at Kwabotwe Hill in the northern part of the town, at the top of Kotokoraba Road in Cape Coast. The school sometimes has been referred to as 'Kwabotwe' for that reason. It has turned out some of the country's best known public figures in all walks of life, men such as Alex Quaison-Sackey, former President of the General Assembly of UN, Dr. K A Busia, Kofi Annan, the immediate past General Secretary of the United Nations. It was deemed to be a Grammar School because Latin and Greek were taught but the school also offered carpentry, art and crafts and it has generally been known as "Mfantsipim School". It was an all boys boarding school although the intake included a small number of "day students", that is, pupils who attended school from home. Girls were later admitted to the sixth form. Today Mfantsipm is an all-boys secondary institution and has historic ties with its sister school, the Wesley Girls' High School. Mfantsipim is affectionately referred to as 'The School' by its alums (old boys) due to the institutions historic origins.

Yaa Asantewaa (c. 1840 – 17 October 1921) (pronounced YAA A-san-TE-WAA) was appointed queen mother of Ejisu of the Ashanti Empire—now part of modern-day Ghana—by her brother Nana Akwasi Afrane Okpese, the Ejisuhene "ruler of Ejisu". In 1900 she led the Ashanti rebellion known as the War of the Golden Stool against British colonialism.

During her brother's reign, Yaa Asantewaa saw the Asante Confederacy go through a series of events that threatened its future, including civil war from 1883 to 1888. When her brother died in 1894, Yaa Asantewaa used her right as Queen Mother to nominate her own grandson as Ejisuhene. When the British exiled him in the Seychelles in 1896, along with the King of Asante Prempeh I and other members of the Asante government, Yaa Asantewaa became regent of the Ejisu-Juaben District. After the deportation of Prempeh I, the British governor-general of the Gold Coast, Frederick Hodgson, demanded the Golden Stool, the symbol of the Asante nation. This request led to a secret meeting of the remaining members of the Asante government at Kumasi, to discuss how to secure the return of their king. There was a disagreement among those present on how to go about this. Yaa Asantewaa, who was present at this meeting, stood and addressed the members of the council with these now-famous words: