Founded in 1881, the school is administered by the Roman Catholic Diocese of Hyderabad in Pakistan.

So the Archbishop of Bombay requested the railway authority to construct a school.

It was run by the Jesuits from 1 October 1888 to 1915 as a primary school, initially for the children of railway personnel, but in 1897 it was opened to all local people.

The school again started receiving financial assistance from the railway on 29 April 1916.

That year, the principal saw the need for a primary Urdu school and on 13 October 1953 it came into existence.

In 1972, Zulfiqar Ali Bhutto, the Prime Minister of Pakistan, nationalized many private educational institutions including St. Mary's.

The newly constructed classrooms proved to be insufficient due to the increase in the number of students.

In April 2006, the convener of the standing committee on minorities of the National Assembly said that repair work on the damaged classrooms of the school would be started within a few days.

[1] In 2010, the sisters of the School organized teams of volunteers to provide cooked food and water for hundreds of people affected by the floods in Sindh province.

[4] On 20 December 2011, Muslim, Hindu, and Christian students collectively organized a single event to celebrate Christmas, Diwali, and Eid in a display of religious solidarity.

Deputy Speaker of Provincial Assembly of Sindh, Mr. Anthony Naveed presided as the Chief Guest.