Sindh Madrasa was founded in 1 September 1885 by Hassan Ali Effendi, a Sindhi of Turkish origin who settled in Karachi. It began to become popular with mainly Muslims of Sindh including Baloch. It is modeled on the British public school system. The founding father of Pakistan, Mohammed Ali Jinnah studied there. Sindh Madressatul Islam is one of the oldest modern Muslim educational institutions in South Asia. It was founded on September 1, 1885 in Karachi, with the objective to impart modern education to the people of Sindh. It was founded by a group of Sindhi Muslim visionaries led by Khan Bahadur Hassan Ali Effendi, the great grandfather of President of Pakistan, Asif Ali Zardari. By 1895, with the untiring efforts of Hassan Ali Effendi, the institution had fully developed into a very well functioning high school with three primary branches that taught in Sindhi. The Quran classes were regularly conducted in the prayer halls.
Sindh Madrasatul Islam was established on the premises of Qafila Serai a former caravan station in Karachi.