Tamale Girls Senior High School was established in 1998/99 academic year as the first Girls Senior High School in Northern Region. The initiative of the establishment of the school was by the RAINS/CAMFED, an international NGO in collaboration with the Regional Co-ordinating Council (RCC) and Ghana Education Service to cater for the pressing needs for female institution in the Region.

The school started with an enrolment of 62 girls with 12 teachers. The programmes of study are General Arts, General Science, Business and Home Economics. With the progression of the school, the enrolment as at 2018/19 stands at 1,328 with 73 teachers and 59 non-teaching staffs respectively.

The first acting Head of the school in 1999 was Mr. Issah Issahaku (INSECT). He was supported by an interim management board.

In the year 2000, the first substantive headmistress of the school Miss Mercy Amanquandoh was appointed. Upon her retirement, the second headmistress, Hajia Mariatu Mohammed took over the administration of the school in January, 2010. She also retired in May, 2014 and the third Headmistress, Hajia Amina M. Musah took over the administration of the school. The 4th Headmistress, Hajia Nafisa Abukari was transferred from Sawla SHS to Tamale Girls SHS as new headmistress in October 2016.