The school was founded in 1951 by the then British Colonial Authorities as the first second cycle institution of the Northern Territories.

[5] The school can count amongst its ranks; a head of State,  two vice presidents of the fourth republic of Ghana, a speaker of parliament, two Justices of the Supreme Court of Ghana, two Chiefs of Defence Staff, and a host of government ministers and members of parliament.

[1][9][10] The main objective of the establishment of the institution amongst others was to mitigate the widening gap of the human resource capacity between the North and the South of the then British Colony.

[12][13][14] As a selective school, admissions are based on the results of applicants in the Basic Education Certificate Examination (BECE).

These students were subsequently afforded the opportunity to pursue further education at the expense of the Central Government.

Some of these students included John S. Nabila who later became Minister for Information and Tourism during the Limann regime.

[17] But as of December 15, 2021, the population of students of Tamale Senior High School was 3,638 with 1,682 females and 1,956 males.

[18] Courses provided by the school at its inception were; English, Mathematics, Science, History, Latin, Geography, Citizenship, Hygiene and Physiology, Agriculture, Music, Arts and Crafts.

The Crafts taught were Cloth Weaving, Book Binding, Leather Work and Pottery.

Students who apply for the school also choose the course they will want to offer prior to writing their BECE examination.

The computerized system subsequently places students not only into the school but also into their preferred course.

2024- Present Yakubu Mohammed Mustapha A number of distinguished citizens who have served the world in a variety of positions have been created by the school over the years.

[23] Alumni of Tamale Senior High School are those old students who have excelled in their various fields of endeavor.