Mfantsiman Girls' Secondary School was formerly known as Saltpond Girls' Secondary School. The name was changed to Mfantsiman when the District of Saltpond became the District of Mfantsiman. The school was founded by the late Osagyefo Dr. Kwame Nkrumah, President of the First Republic of Ghana as a special gesture of appreciation to the people of Saltpond for the part the town played in the political history of the country. His aim was to empower girls in the area and in addition establish a Polytechnic for girls.
A group of prominent persons were selected to choose the site for the School, and this team were made up as follows: Mr. Kojo Botsio, Minister of Education, Mr. Kofi Baako, Member of Parliament of Saltpond, Mr. George Padmore, West Indian Pan-Africanist, Dr. Hastins Banda, President of the Republic of Malawi, and Mr. S.E. Arthur, Member of the School Board of Governors. The area where the school is established used to be called Kuntupow. Constructional work of the school thus began in 1958 on a land size measuring 430.10 acres. Part of the first phase consisted of the Administration Block, Classroom Block, Science Block, Dining Hall, one teacher's bungalow and the headmistress's bungalow were completed in September 1960.
On 23 September 1960, students were selected through the late Entrance Examination and interviews, and on 30 September 1960, the school was made one of the Ghana Education Trust (GET) schools, and opened its gates to its first students comprising of a batch of seventy (70) and four (4) teachers including the Headmistress. The first two dormitory blocks Chinery and Butler Houses (named respectively after the Headmistress and the Assistant Headmistress at the time - a tradition that was continued by their predecessors) were completed in 1961, and the students moved from their temporary top Classroom Block dormitories to take up occupancy. There were 140 students at the time. The school uniform was green in colour but was later changed to the mauve used up until now. The anthem of the school was a latin song which is still used by KNUST as its anthem, and it goes like: Gaudeamus Igitor, Juvenesdum Sumus, Post Jucundem, Juvestutem, Pre Molestem Senectutem, Nos Habis Humus. Meaning: Let us rejoice now that we are young. For after youth comes old age. Before death is senility. Let us rejoice now that we have life.
In June 1965 the first batch of fifth (5th) formers took the General Certificate of Education (GCE). There are Fifty-one (51) candidates in all and thirty-four (34) had GCE passes (66.7 per cent). Between 1964 and 1967, the second phase of the school construction was completed during this time, namely a third dormitory block - Engmann House and the first block of staff flats was also completed. The school's overhead water tank connected to Baifikrom Water Works, because of the erratic nature of the Brimso water supply. The school also got the school linked with the Akosombo electricity grid. In 1968, the sixth (6th) form Arts and Science faculties were started. Initially there was a problem getting girls to take Science subjects, so between September 1969 and June 1976 boys were admitted to the sixth (6th) form to take Science (She-boys).
A third stream was opened in 1974, and a number of staff bungalows were built between the School Block and the Headmistress's bungalow. A fourth dormitory block - Scotton House was also added. During the late 1970's a primary school and a well-equipped staff club was planned to help in stemming the frequent turnover in the teaching staff. In the interim a play school for teachers' children was started by Mrs. Park, spouse of one of the expartriate teachers to meet this void. There was a markedly improvement in the academic field, good discipline and a firm Parent/Teacher Association was established. In the early 80's the primary school finally became a reality, when the Canadian High Commission in Accra responded to the school's appeal and made available the sum of 1,955,488.44 Cedis for the construction of a permanent building for the primary school. A fifth dormitory, Croffie House was constructed by the PTA in 1998 to alleviate the acute accommodation shortage the school experienced as a result of a rapid increase in the student populace. This house was named after Mrs. Elizabeth Croffie the incumbent Headmistress at the time. A recent addition to the block of dormitories in 2009 is Yeboah House named after the late Mrs. Vida Yeboah (former Headmistress).
Since its inception half a century ago, the School has turned out over 10,000 students (including 18 boys) with School Certificates/General Certificate of Education Ordinary Level, Advanced Level Certificates and Senior Secondary School Certificates. Most of these products have become prominent members of society and serve as bankers, business women, doctors, district directors and secretaries, headmasters and headmistresses. Others are members of parliament, ministers of state, pharmacists, undergraduates in tertiary institutions and university lecturers.