The school, the first second cycle institution in Ashanti was established in 1937 by the late J.T. Robert who was a Sierra Leonean. The school operated under the name Asante Collegiate and was sited at Asafo, a suburb of Kumasi.
In September, 1962, it was taken over by the Ministry of Education but was still under the name Asante Collegiate. At the beginning of the, 1968/69 academic year, the school as renamed after the late Sir Osei Agyemang Prempeh II, known in private life as Barima Kwame Kyeretwie in his honour.
Shortly after the re-naming ceremony, the school moved to a new site at Dichemso formerly occupied by Modern City Academy form then on, the school witnessed rapid exponential growth in population and as a result of this; a new site was acquired at Old Tafo by Nana Kwame Kyeretwie himself. A committee was set up through the lands commission to demarcate the site in 1970. In 1979, the school started operating at the two sites. This was not easy at all. The operational cost was heavy besides the risk of transporting students to and from the two sites on daily basis. The school eventually moved to new site at Old Tafo, Kumasi in 2004/05 academic year.
As a result of gradual encroachment on the land, the President by an Executive Instrument compulsorily acquired the land in 1998-168.28 acreage.