As an Methodist-Presbyterian school, Prempeh College aims to deepen an awareness of the love of God and to encourage spiritual growth. Whilst boys of other denominations and faiths are welcomed, all pupils are required to attend religion classes, daily acts of worship and certain other compulsory chapel services which are taken by the full-time Chaplain.

However, in a recent interview, Rev. S.N. Pearson, the founding Headmaster, revealed that, "the school was run on a Christian basis but was open to people of all faiths and none. There was always a Sunday evening service which was taken by members of staff or visitors to the school. Attendance was optional but all the boys chose to attend as well as some members of the public from Kumasi."

Other services, including confirmation and Carols, are celebrated regularly; these provide ample opportunity for boys to further their worship. The Sunday services are compulsory for boarders. Boys are encouraged to participate actively in the worship. Many serve in other ways as Chaplains prefects, Chaplain Assistants, servers or choir members.