St. Joseph's College for Women was founded on June 21, 1948 by Sister Mary Alban, a member of the Religious Congregation - The Institute of the Daughters of the Cross. Pakistan had just been created and the new nation required more institutions for the promotion of education. The College was set up to promote and accelerate the higher education of the women of Karachi. It was started in the already existing St. Joseph's Convent School by making a few of its classrooms available for the College students. Sister Mary Alban, the founder of the College, was appointed its first Principal and the College was affiliated with the Sindh University.

St. Joseph's have demonstrated outstanding performance obtaining merit positions in both the Intermediate Board and Karachi University Examinations in all the programs of study offered by the College. Their outstanding performance has also been reflected in various co-curricular activities. On the sports field the College has been a regular recipient of the General Championship of the Inter-Collegiate Tournaments winning the volleyball, table tennis, badminton, throw-ball and athletics competitions. They have also excelled in both English and Urdu debates and declamation contests held at both the Intermediate and University levels.