The school was founded on 22 January 1940 by the late Rev. Dr. A. W. E. Appiah with six boys. He named the school Aggrey Memorial College after his late Uncle Dr. J. E. Kwegyir Aggrey. His aim was to perpetuate the memory of his uncle by means of an institution, which would give young boys and girls adequate secondary education which would fit them into higher fields of learning. The School is thus a living tribute to that great son of Africa - - Dr. Kwegyir Aggrey.
During the first few years, the school occupied, successively, buildings in the heart of Cape Coast Township, in the Central Region of Ghana. The first home was called "Tandon Kuma", House Number 39, Jukwa Road, which also serve as the Headmaster’s residence. The rent was two pounds (£2) five shillings (5sh) a month.
In April, 1940, with an enrolment of ten boys, the school moved to "Bucknor Villa" with a rent of two pounds a month but due to unhealthy conditions, the school moved to yet another house rented by a football team on 1st November. The rent this time was six shillings. By this time, there were 20 boys – nine of them were in the preparatory class.
The School went on the first Christmas holidays on 10 December 1940 and resumed on 21 January 1941 to meet another misfortune. Just a day to the re-opening, dark ominous clouds gathered but the school stood firm, the football team decided not to share the premises with the school thus the second year was started in the Headmaster’s residence at House Number 40, Royal Lane, Cape Coast with nine boys. This later reduced to five in the second term. The year 1941 ended with the school well shaken and battered but the founder was undaunted.
On 8 February 1943, the school moved to yet another house, No. C50/1, Commissioner Road, Cape Coast, owing to the growing number of students. The rent for this facility was three pounds, five shillings per month. The founder established the primary and intermediary section of the school in this year to buttress the Secondary Department of the school.
On 1 October 1943, with an enrolment well beyond two hundred students, the top section of the school (i.e. Standard 3, Intermediate and Secondary Department) moved to the sixth home of the school at Old Swanzy Factory at No.1 Royal Lane, which belonged to the United African Company (UAC).
Up to this time, the headmaster was the only member of staff. In January, 1944, however, Mr. Henry Abaidoo-Brew was appointed the first Assistant Headmaster of the school. With the schools in dire need of financial assistance, the late Mr. Kofi Bentsi-Enchill, a Cape Coast merchant, very generously offered to pay the salary of the Assistant Head Master and the rent for the premises.
In 1945, a Board of Trustees and Management team known as the "Aggrey Society" was formed and the school’s management came under this Board. Members of the Board were Mr. Kofi Bentsi-Enchill (Chairman), Dr. J. W. de Graft-Johnson, Mr. W. W. O. Lindsay, Mr. J. Magnus Sampson, Mr. S. S. Wood and Chief Kweku Egyir Gyepi, II and under the management of this Society, the Secondary Department of the school was separated from the Primary Department In February, 1946.
Within this period that the school managed to be in existence, students were attracted from all places including particularly those who had been to other schools before but wished to improve their grades.
In 1947, the African Methodist Episcopal (A.M.E.) Zion Church took over the realm of affairs of the school as a result of an agreement between the "Aggrey Society" and the A.M.E. Zion Mission. The name of the school was then changed from "Aggrey Memorial College" to Aggrey Memorial A.M.E. Zion Secondary School", and the first two boarders were also admitted. That year, the founder also enrolled his own fresh students to the Secondary department of the school. These were six boys who were later presented for the Cambridge School Certificate Examination (CSCE) in 1950. All of them passed with one achieving exemption from London Matriculation.
The School moved in October, 1948 to a three-storey building on the premises of the old Cape Coast Post Office near the Cape Coast Castle. The School occupied this building known as "Old Russell" from 1948 to 1958. In 1958, the A.M.E. Zion Church acquired a 43-acre land, released as a Deed of Gift by the then Nana Attobra of the Nsona Stool Family of Brafo Yaw, to the school.
In 1952, the school entered an important landmark; the A.M.E. Zion Church commenced the building of the first block on the site. The school was recognized as "Encouraged Secondary School" in receipt of Government grant in aid. A new beginning was made in that year and since that time the story of Aggrey Memorial A.M.E. Zion Secondary School has been one of steady progress and improvement. The number of students increasing year on year.
After eighteen years in temporary premises, the school moved to its present site near Brafo Yaw, Cape Coast in January, 1958. Girls in the boarding house were however housed in Cape Coast Township on premises formerly occupied by the "Prospect Printing Press". On 21 January 1966 the girls moved into their new dormitory block across the boys from the Accra-Takoradi road at Brafo Yaw.
In 1991 the school also started the educational reform programme which saw the coming into being of the Senior Secondary Programme. Alongside the Ordinary and Advanced levels programmes.
The school has also chalked a first in being the only second cycle school in the country to have fully computerized and networked its administrative system. The school also runs a computer literacy class for all students in the school to prepare them for the new world they would be entering after their schooling.